17-12722936-C-T

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_001146312.3(MYOCD):c.343C>T(p.Arg115Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MYOCD NM_001146312.3 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:2
• Conservation: PhyloP100: 1.78

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 Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 17-12722936-C-T is Pathogenic according to our data. Variant chr17-12722936-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 689480.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYOCD	NM_001146312.3	c.343C>T	p.Arg115Ter	stop_gained	5/14	ENST00000425538.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYOCD	ENST00000425538.6	c.343C>T	p.Arg115Ter	stop_gained	5/14	1	NM_001146312.3	P2
MYOCD	ENST00000343344.8	c.343C>T	p.Arg115Ter	stop_gained	5/13	1		A2
MYOCD	ENST00000395988.1	n.263C>T		non_coding_transcript_exon_variant	2/9	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1461810 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727212

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

Submissions by phenotype

Prune belly syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

research

Department of Medical Biology, Academic Medical Center

May 01, 2019

- -

Megabladder, congenital Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Dec 23, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.58	D
BayesDel_noAF	Pathogenic	0.60
Cadd	Pathogenic	38
Dann	Uncertain	1.0
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.90	D
MutationTaster	Benign	1.0	A;A;A
Vest4		0.79
GERP RS		3.2

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: rs1597782599; hg19: chr17-12626253; COSMIC: COSV58504210;