17-12744173-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.718-10T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.833 in 1,612,934 control chromosomes in the GnomAD database, including 562,590 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.81 (49894 hom., cov: 32)
  • Exomes 𝑓: 0.84 (512696 hom.)
• Consequence: MYOCD NM_001146312.3 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0001284
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.102

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=-0.84).
• BP6: Variant 17-12744173-T-C is Benign according to our data. Variant chr17-12744173-T-C is described in ClinVar as [Benign]. Clinvar id is 1181987.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYOCD	NM_001146312.3	c.718-10T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000425538.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYOCD	ENST00000425538.6	c.718-10T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001146312.3	P2
MYOCD	ENST00000343344.8	c.718-10T>C		splice_polypyrimidine_tract_variant, intron_variant		1		A2
MYOCD	ENST00000395988.1	n.638-10T>C		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.808 AC: 122798 AN: 152064 Hom.: 49859 Cov.: 32

Gnomad AFR AF: 0.747

Gnomad AMI AF: 0.840

Gnomad AMR AF: 0.735

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.731

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.895

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.859

Gnomad OTH AF: 0.817

GnomAD3 exomes AF: 0.805 AC: 199852 AN: 248364 Hom.: 81140 AF XY: 0.808 AC XY: 108644 AN XY: 134466

Gnomad AFR exome AF: 0.747

Gnomad AMR exome AF: 0.685

Gnomad ASJ exome AF: 0.760

Gnomad EAS exome AF: 0.750

Gnomad SAS exome AF: 0.747

Gnomad FIN exome AF: 0.899

Gnomad NFE exome AF: 0.860

Gnomad OTH exome AF: 0.820

GnomAD4 exome AF: 0.836 AC: 1221134 AN: 1460752 Hom.: 512696 Cov.: 52 AF XY: 0.833 AC XY: 605580 AN XY: 726632

Gnomad4 AFR exome AF: 0.743

Gnomad4 AMR exome AF: 0.690

Gnomad4 ASJ exome AF: 0.763

Gnomad4 EAS exome AF: 0.707

Gnomad4 SAS exome AF: 0.744

Gnomad4 FIN exome AF: 0.902

Gnomad4 NFE exome AF: 0.856

Gnomad4 OTH exome AF: 0.820

GnomAD4 genome AF: 0.807 AC: 122883 AN: 152182 Hom.: 49894 Cov.: 32 AF XY: 0.805 AC XY: 59923 AN XY: 74422

Gnomad4 AFR AF: 0.747

Gnomad4 AMR AF: 0.735

Gnomad4 ASJ AF: 0.762

Gnomad4 EAS AF: 0.731

Gnomad4 SAS AF: 0.741

Gnomad4 FIN AF: 0.895

Gnomad4 NFE AF: 0.859

Gnomad4 OTH AF: 0.813

Alfa AF: 0.839 Hom.: 61379

Bravo AF: 0.795

Asia WGS AF: 0.714 AC: 2485 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	-0.84
Cadd	Benign	11
Dann	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00013
dbscSNV1_RF	Benign	0.016
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: rs12709295; hg19: chr17-12647490; COSMIC: COSV58513050; COSMIC: COSV58513050;