15-57667430-T-C

Position:

• chr15-57667430-T-C

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYZAP	NM_001018100.5	c.1203+5897T>C		intron_variant		ENST00000267853.10
GCOM1	NR_104367.2	n.1867+5897T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYZAP	ENST00000267853.10	c.1203+5897T>C		intron_variant		1	NM_001018100.5	P1
MYZAP	ENST00000380565.8	c.1120-7538T>C		intron_variant		1
MYZAP	ENST00000461709.1	c.348+5897T>C		intron_variant		3

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

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.784

Gnomad4 ASJ AF: 0.815

Gnomad4 EAS AF: 0.652

Gnomad4 SAS AF: 0.725

Gnomad4 FIN AF: 0.826

Gnomad4 NFE AF: 0.838

Gnomad4 OTH AF: 0.727

Alfa AF: 0.810 Hom.: 65022

Bravo AF: 0.671

Asia WGS AF: 0.649 AC: 2262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	10
DANN	Benign	0.61

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: rs1559776; hg19: chr15-57959628;