rs937254

Positions:

• chr15-57617966-G-A
• chr15-57617966-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001018100.5(MYZAP):​c.163-67G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 1,539,032 control chromosomes in the GnomAD database, including 141,119 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.47 (17324 hom., cov: 32)
  • Exomes 𝑓: 0.42 (123795 hom.)
• Consequence: MYZAP NM_001018100.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99

Genes affected

MYZAP (HGNC:43444): (myocardial zonula adherens protein) This gene encodes a protein that is abundantly expressed in cardiac tissue. The encoded protein localizes to intercalated discs in cardiomyocytes and functions as an activator of Rho-dependent serum-response factor signaling. Alternative splicing results in multiple transcript variants. Readthrough transcription also exists between this gene and the neighboring downstream gene POLR2M (polymerase (RNA) II (DNA directed) polypeptide M) and is represented with GeneID: 145781. [provided by RefSeq, Mar 2014]

GCOM1 (HGNC:26424): (GCOM1, MYZAP-POLR2M combined locus) 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]

GCOM1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYZAP	NM_001018100.5	c.163-67G>A		intron_variant		ENST00000267853.10	NP_001018110.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYZAP	ENST00000267853.10	c.163-67G>A		intron_variant		1	NM_001018100.5	ENSP00000267853.5
GCOM1	ENST00000587652.5	c.163-67G>A		intron_variant		2		ENSP00000465231.1

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71357 AN: 151894 Hom.: 17307 Cov.: 32

Gnomad AFR AF: 0.573

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.463

GnomAD4 exome AF: 0.417 AC: 578843 AN: 1387020 Hom.: 123795 AF XY: 0.420 AC XY: 287344 AN XY: 683600

Gnomad4 AFR exome AF: 0.586

Gnomad4 AMR exome AF: 0.611

Gnomad4 ASJ exome AF: 0.417

Gnomad4 EAS exome AF: 0.534

Gnomad4 SAS exome AF: 0.564

Gnomad4 FIN exome AF: 0.427

Gnomad4 NFE exome AF: 0.391

Gnomad4 OTH exome AF: 0.431

GnomAD4 genome AF: 0.470 AC: 71426 AN: 152012 Hom.: 17324 Cov.: 32 AF XY: 0.475 AC XY: 35322 AN XY: 74284

Gnomad4 AFR AF: 0.573

Gnomad4 AMR AF: 0.541

Gnomad4 ASJ AF: 0.415

Gnomad4 EAS AF: 0.560

Gnomad4 SAS AF: 0.558

Gnomad4 FIN AF: 0.418

Gnomad4 NFE AF: 0.390

Gnomad4 OTH AF: 0.461

Alfa AF: 0.416 Hom.: 17868

Bravo AF: 0.483

Asia WGS AF: 0.531 AC: 1850 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0010
DANN	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs937254; hg19: chr15-57910164; COSMIC: COSV51089983;