17-12739573-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001146312.3(MYOCD):c.717+245T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 152,114 control chromosomes in the GnomAD database, including 20,424 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.52 (20424 hom., cov: 33)
• Consequence: MYOCD NM_001146312.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.05

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 17-12739573-T-C is Benign according to our data. Variant chr17-12739573-T-C is described in ClinVar as [Benign]. Clinvar id is 1264358.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYOCD	NM_001146312.3	c.717+245T>C		intron_variant		ENST00000425538.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYOCD	ENST00000425538.6	c.717+245T>C		intron_variant		1	NM_001146312.3	P2
MYOCD	ENST00000343344.8	c.717+245T>C		intron_variant		1		A2
MYOCD	ENST00000395988.1	n.637+245T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78540 AN: 151996 Hom.: 20412 Cov.: 33

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.562

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.517 AC: 78580 AN: 152114 Hom.: 20424 Cov.: 33 AF XY: 0.516 AC XY: 38405 AN XY: 74362

Gnomad4 AFR AF: 0.497

Gnomad4 AMR AF: 0.469

Gnomad4 ASJ AF: 0.484

Gnomad4 EAS AF: 0.641

Gnomad4 SAS AF: 0.562

Gnomad4 FIN AF: 0.564

Gnomad4 NFE AF: 0.522

Gnomad4 OTH AF: 0.495

Alfa AF: 0.513 Hom.: 31922

Bravo AF: 0.511

Asia WGS AF: 0.573 AC: 1992 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.94
Cadd	Benign	0.94
Dann	Benign	0.71

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: rs11657113; hg19: chr17-12642890; COSMIC: COSV58500292; COSMIC: COSV58500292;