chr17-12717580-G-A

Position:

• chr17-12717580-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001146312.3(MYOCD):​c.253+159G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.758 in 152,086 control chromosomes in the GnomAD database, including 43,908 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.76 (43908 hom., cov: 32)
• Consequence: MYOCD NM_001146312.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.560

Genes affected

MYOCD (HGNC:16067): (myocardin) This gene encodes a nuclear protein, which is expressed in heart, aorta, and in smooth muscle cell-containing tissues. It functions as a transcriptional co-activator of serum response factor (SRF) and modulates expression of cardiac and smooth muscle-specific SRF-target genes, and thus may play a crucial role in cardiogenesis and differentiation of the smooth muscle cell lineage. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 17-12717580-G-A is Benign according to our data. Variant chr17-12717580-G-A is described in ClinVar as [Benign]. Clinvar id is 1229503.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYOCD	NM_001146312.3	c.253+159G>A		intron_variant		ENST00000425538.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYOCD	ENST00000425538.6	c.253+159G>A		intron_variant		1	NM_001146312.3	P2
MYOCD	ENST00000343344.8	c.253+159G>A		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.758 AC: 115156 AN: 151966 Hom.: 43870 Cov.: 32

Gnomad AFR AF: 0.703

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.735

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.798

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.800

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.791

Gnomad OTH AF: 0.754

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

GnomAD4 genome AF: 0.758 AC: 115245 AN: 152086 Hom.: 43908 Cov.: 32 AF XY: 0.756 AC XY: 56200 AN XY: 74324

Gnomad4 AFR AF: 0.704

Gnomad4 AMR AF: 0.735

Gnomad4 ASJ AF: 0.737

Gnomad4 EAS AF: 0.799

Gnomad4 SAS AF: 0.716

Gnomad4 FIN AF: 0.800

Gnomad4 NFE AF: 0.791

Gnomad4 OTH AF: 0.751

Alfa AF: 0.775 Hom.: 61079

Bravo AF: 0.751

Asia WGS AF: 0.742 AC: 2582 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.12
DANN	Benign	0.73

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: rs12602716; hg19: chr17-12620897;