15-57667430-T-C

Variant names:

• chr15-57667430-T-C
• rs1559776
• NM_001018100.5:c.1203+5897T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001018100.5(MYZAP):​c.1203+5897T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 152,056 control chromosomes in the GnomAD database, including 39,346 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 0.69 (39346 hom., cov: 31)
• Consequence: MYZAP NM_001018100.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.49
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• dilated cardiomyopathy

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001018100.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYZAP	NM_001018100.5	MANE Select	c.1203+5897T>C		intron	N/A	NP_001018110.1	P0CAP1-1
	GCOM1	NM_001285900.3		c.1203+5897T>C		intron	N/A	NP_001272829.1	H8Y6P7
	GCOM1	NM_001018090.6		c.1203+5897T>C		intron	N/A	NP_001018100.1	P0CAP1-11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYZAP	ENST00000267853.10	TSL:1 MANE Select	c.1203+5897T>C		intron	N/A	ENSP00000267853.5	P0CAP1-1
	GCOM1	ENST00000587652.5	TSL:2	c.1203+5897T>C		intron	N/A	ENSP00000465231.1	H8Y6P7
	MYZAP	ENST00000380565.8	TSL:1	c.1120-7538T>C		intron	N/A	ENSP00000369939.4	P0CAP1-4

Frequencies

GnomAD3 genomes AF: 0.686 AC: 104231 AN: 151938 Hom.: 39346 Cov.: 31

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.897

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.815

Gnomad EAS AF: 0.653

Gnomad SAS AF: 0.724

Gnomad FIN AF: 0.826

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.838

Gnomad OTH AF: 0.731

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.686 AC: 104249 AN: 152056 Hom.: 39346 Cov.: 31 AF XY: 0.687 AC XY: 51095 AN XY: 74340

African (AFR) AF: 0.345 AC: 14292 AN: 41434

American (AMR) AF: 0.784 AC: 11974 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.815 AC: 2829 AN: 3472

East Asian (EAS) AF: 0.652 AC: 3364 AN: 5160

South Asian (SAS) AF: 0.725 AC: 3494 AN: 4820

European-Finnish (FIN) AF: 0.826 AC: 8743 AN: 10590

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.838 AC: 56990 AN: 67990

Other (OTH) AF: 0.727 AC: 1532 AN: 2106

Alfa AF: 0.784 Hom.: 142046

Bravo AF: 0.671

Asia WGS AF: 0.649 AC: 2262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	10
DANN	Benign	0.61
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1559776; hg19: chr15-57959628;