PLAC8L1

Chr 5

PLAC8 like 1

NCBI Gene: 153770 ENSG00000173261 UniProt: A1L4L8

I cannot write a clinical gene summary for PLAC8L1 because the provided information lacks essential details about the protein's function, associated diseases, and inheritance patterns. While the data suggests gain-of-function mutations may be pathogenic and the gene appears tolerant to loss-of-function variants, no specific neurological conditions or clinical phenotypes are described that would be relevant for a pediatric neurogenetics portal.

ResearchSummary from Mechanism

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.31

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.31LOEUF

pLI 0.008

Z-score 1.04

OE 0.57 (0.28–1.31)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.86Z-score

OE missense 0.76 (0.63–0.92)

77 obs / 101.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.57 (0.28–1.31)

0≤0.351.4

Missense OE?0.76 (0.63–0.92)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 4 / 7.0Missense obs/exp: 77 / 101.3Syn Z: -0.16

Background carrier burden — how many people carry a rare variant somewhere in PLAC8L1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 170

195 rare PASS variants

Rare truncating (LoF)

1 in 5,300

34 rare PASS variants

Rare synonymous (reference)

1 in 190

81 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PLAC8L1. 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 280	1 in 6,200
South Asian	~43k	1 in 260	1 in 3,300
Remaining (unassigned)	~30k	1 in 220	1 in 6,000
European (Finnish)	~27k	1 in 570	≈ 1 in 27,000
Admixed American	~22k	1 in 300	≈ 1 in 5,700
African / African American	~21k	1 in 150	1 in 2,900
East Asian	~20k	1 in 480	≈ 1 in 5,000
Ashkenazi Jewish	~13k	1 in 690	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 240	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): All 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓