17-12735977-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.416-184T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 152,110 control chromosomes in the GnomAD database, including 21,598 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.53 (21598 hom., cov: 33)
• Consequence: MYOCD NM_001146312.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.74

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=-0.91).
• BP6: Variant 17-12735977-T-C is Benign according to our data. Variant chr17-12735977-T-C is described in ClinVar as [Benign]. Clinvar id is 1220717.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYOCD	NM_001146312.3	c.416-184T>C		intron_variant		ENST00000425538.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYOCD	ENST00000425538.6	c.416-184T>C		intron_variant		1	NM_001146312.3	P2
MYOCD	ENST00000343344.8	c.416-184T>C		intron_variant		1		A2
MYOCD	ENST00000395988.1	n.336-184T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80217 AN: 151992 Hom.: 21581 Cov.: 33

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.540

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.858

Gnomad SAS AF: 0.660

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.499

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

GnomAD4 genome AF: 0.528 AC: 80268 AN: 152110 Hom.: 21598 Cov.: 33 AF XY: 0.534 AC XY: 39685 AN XY: 74364

Gnomad4 AFR AF: 0.511

Gnomad4 AMR AF: 0.586

Gnomad4 ASJ AF: 0.514

Gnomad4 EAS AF: 0.858

Gnomad4 SAS AF: 0.660

Gnomad4 FIN AF: 0.555

Gnomad4 NFE AF: 0.488

Gnomad4 OTH AF: 0.502

Alfa AF: 0.495 Hom.: 25126

Bravo AF: 0.530

Asia WGS AF: 0.742 AC: 2579 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	-0.91
Cadd	Benign	0.062
Dann	Benign	0.27

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: rs1465249; hg19: chr17-12639294; COSMIC: COSV58500287;