GCOM1

Chr 15AR

GCOM1, MYZAP-POLR2M combined locus

Also known as: GRINL1A, Gcom2, MYZAP-POLR2M, gcom

NCBI Gene: 145781 ENSG00000137878 OMIM: 614071

This locus represents naturally occurring readthrough transcription between the neighboring MYZAP (myocardial zonula adherens protein) and POLR2M (polymerase (RNA) II (DNA directed) polypeptide M) genes on chromosome 15. Alternative splicing results in multiple readthrough transcript variants. Readthrough variants may encode proteins that share sequence identity with the upstream gene product or with both the upstream and downstream gene products. Some readthrough transcript variants are also expected to be candidates for nonsense-mediated decay (NMD). [provided by RefSeq, Oct 2013]

OMIM Research

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Cardiomyopathy, dilated, 2KMIM #620894

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Cardiomyopathy, dilated, 2K; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.20

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.20LOEUF

pLI 0.000

Z-score 0.63

OE 0.89 (0.67–1.20)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.86Z-score

OE missense 1.14 (1.04–1.25)

326 obs / 285.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.89 (0.67–1.20)

0≤0.351.4

Missense OE?1.14 (1.04–1.25)

0≤0.61.4

Synonymous OE?1.30

0≤1.21.6

LoF obs/exp: 31 / 35.0Missense obs/exp: 326 / 285.0Syn Z: -2.47

Background carrier burden — how many people carry a rare variant somewhere in GCOM1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 49

1,052 rare PASS variants

Rare truncating (LoF)

1 in 1,000

150 rare PASS variants

Rare synonymous (reference)

1 in 100

406 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GCOM1. 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 75	1 in 1,200
South Asian	~43k	1 in 36	1 in 930
Remaining (unassigned)	~30k	1 in 37	1 in 1,100
European (Finnish)	~27k	1 in 200	1 in 1,500
Admixed American	~22k	1 in 35	1 in 1,600
African / African American	~21k	1 in 40	1 in 860
East Asian	~20k	1 in 56	1 in 540
Ashkenazi Jewish	~13k	1 in 410	none seen
Middle Eastern	~2,884	1 in 38	≈ 1 in 1,400

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): 14 of 15 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 15.? see exons ↓