17-12715363-G-C

Position:

• chr17-12715363-G-C

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.122-156G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 151,994 control chromosomes in the GnomAD database, including 1,396 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.13 (1396 hom., cov: 32)
• Consequence: MYOCD NM_001146312.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.777

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=-0.61).
• BP6: Variant 17-12715363-G-C is Benign according to our data. Variant chr17-12715363-G-C is described in ClinVar as [Benign]. Clinvar id is 1265097.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYOCD	NM_001146312.3	c.122-156G>C		intron_variant		ENST00000425538.6	NP_001139784.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYOCD	ENST00000425538.6	c.122-156G>C		intron_variant		1	NM_001146312.3	ENSP00000401678.1
MYOCD	ENST00000343344.8	c.122-156G>C		intron_variant		1		ENSP00000341835.4
MYOCD	ENST00000579237.5	n.*40-156G>C		intron_variant		4		ENSP00000462694.1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19587 AN: 151876 Hom.: 1388 Cov.: 32

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.0889

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0586

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.0818

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.129 AC: 19628 AN: 151994 Hom.: 1396 Cov.: 32 AF XY: 0.127 AC XY: 9416 AN XY: 74306

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.0888

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.0586

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.0818

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.124

Alfa AF: 0.0450 Hom.: 35

Bravo AF: 0.130

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	clinical testing	GeneDx	Jun 20, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	10
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs72811294; hg19: chr17-12618680; COSMIC: COSV58511678; COSMIC: COSV58511678;