SNAPC5

Chr 15

small nuclear RNA activating complex polypeptide 5

Also known as: SNAP19

NCBI Gene: 10302 ENSG00000174446 UniProt: O75971 OMIM: 605979

The protein is a subunit of the SNAPc complex that binds to promoter elements and recruits transcription factors required for RNA polymerase II and III transcription of small nuclear RNA genes. This gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 1.89), suggesting mutations would likely cause severe developmental disorders, though no specific disease associations have been established. The critical role in basic transcriptional machinery suggests that pathogenic variants would probably affect multiple organ systems during early development.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a subunit of the small nuclear RNA (snRNA)-activating protein complex that plays a role in the transcription of snRNA genes. This complex binds to the promoters of snRNA genes transcribed by either RNA polymerase II or III and recruits other regulatory factors to activate snRNA gene transcription. The encoded protein may play a role in stabilizing this complex. A pseudogene of this gene has been identified on chromosome 6. [provided by RefSeq, Jul 2016]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.89

LOEUF

GOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.89LOEUF

pLI 0.000

Z-score -0.43

OE 1.23 (0.61–1.89)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.72Z-score

OE missense 1.28 (1.05–1.58)

66 obs / 51.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.23 (0.61–1.89)

0≤0.351.4

Missense OE?1.28 (1.05–1.58)

0≤0.61.4

Synonymous OE?1.30

0≤1.21.6

LoF obs/exp: 5 / 4.1Missense obs/exp: 66 / 51.4Syn Z: -1.12

Background carrier burden — how many people carry a rare variant somewhere in SNAPC5?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 140

210 rare PASS variants

Rare truncating (LoF)

1 in 3,300

47 rare PASS variants

Rare synonymous (reference)

1 in 800

84 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SNAPC5. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 170	1 in 5,200
South Asian	~43k	1 in 100	1 in 1,300
Remaining (unassigned)	~30k	1 in 250	1 in 5,800
European (Finnish)	~27k	1 in 620	1 in 4,300
Admixed American	~22k	1 in 110	1 in 1,600
African / African American	~21k	1 in 210	≈ 1 in 5,200
East Asian	~20k	1 in 180	1 in 1,000
Ashkenazi Jewish	~13k	≈ 1 in 6,500	none seen
Middle Eastern	~2,884	1 in 280	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.