SCG3

Chr 15

secretogranin III

Also known as: SGIII

NCBI Gene: 29106 ENSG00000104112 UniProt: Q8WXD2 OMIM: 611796

The protein encoded by this gene is a member of the chromogranin/secretogranin family of neuroendocrine secretory proteins. Granins may serve as precursors for biologically active peptides. Some granins have been shown to function as helper proteins in sorting and proteolytic processing of prohormones; however, the function of this protein is unknown. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.66

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.66LOEUF

pLI 0.001

Z-score 2.82

OE 0.38 (0.23–0.66)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.36Z-score

OE missense 0.93 (0.84–1.04)

220 obs / 235.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.38 (0.23–0.66)

0≤0.351.4

Missense OE?0.93 (0.84–1.04)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 9 / 23.8Missense obs/exp: 220 / 235.3Syn Z: -0.30

Background carrier burden — how many people carry a rare variant somewhere in SCG3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 150

563 rare PASS variants

Rare truncating (LoF)

1 in 2,000

84 rare PASS variants

Rare synonymous (reference)

1 in 460

190 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SCG3. 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 520
South Asian	~43k	1 in 78	1 in 560
Remaining (unassigned)	~30k	1 in 110	1 in 2,000
European (Finnish)	~27k	1 in 310	≈ 1 in 6,700
Admixed American	~22k	1 in 190	1 in 2,700
African / African American	~21k	1 in 170	1 in 460
East Asian	~20k	1 in 140	1 in 1,300
Ashkenazi Jewish	~13k	1 in 240	1 in 990
Middle Eastern	~2,884	1 in 140	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.

Exome coverage (gnomAD): 9 of 12 coding exons well covered in gnomAD exomes; exons 2, 8, 11 marginal. Genomes: all 12.? see exons ↓