17-12717444-A-G

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.253+23A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 1,587,076 control chromosomes in the GnomAD database, including 467,080 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.74 (41997 hom., cov: 32)
  • Exomes 𝑓: 0.77 (425083 hom.)
• Consequence: MYOCD NM_001146312.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.922

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=-0.83).
• BP6: Variant 17-12717444-A-G is Benign according to our data. Variant chr17-12717444-A-G is described in ClinVar as [Benign]. Clinvar id is 1225489.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYOCD	NM_001146312.3	c.253+23A>G		intron_variant		ENST00000425538.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYOCD	ENST00000425538.6	c.253+23A>G		intron_variant		1	NM_001146312.3	P2
MYOCD	ENST00000343344.8	c.253+23A>G		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.740 AC: 112405 AN: 151944 Hom.: 41962 Cov.: 32

Gnomad AFR AF: 0.705

Gnomad AMI AF: 0.716

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.732

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.770

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.788

Gnomad OTH AF: 0.737

GnomAD3 exomes AF: 0.727 AC: 179778 AN: 247210 Hom.: 66137 AF XY: 0.732 AC XY: 97650 AN XY: 133420

Gnomad AFR exome AF: 0.701

Gnomad AMR exome AF: 0.563

Gnomad ASJ exome AF: 0.720

Gnomad EAS exome AF: 0.710

Gnomad SAS exome AF: 0.692

Gnomad FIN exome AF: 0.775

Gnomad NFE exome AF: 0.784

Gnomad OTH exome AF: 0.736

GnomAD4 exome AF: 0.768 AC: 1101703 AN: 1435014 Hom.: 425083 Cov.: 24 AF XY: 0.766 AC XY: 547802 AN XY: 715170

Gnomad4 AFR exome AF: 0.698

Gnomad4 AMR exome AF: 0.564

Gnomad4 ASJ exome AF: 0.720

Gnomad4 EAS exome AF: 0.723

Gnomad4 SAS exome AF: 0.689

Gnomad4 FIN exome AF: 0.781

Gnomad4 NFE exome AF: 0.787

Gnomad4 OTH exome AF: 0.762

GnomAD4 genome AF: 0.740 AC: 112482 AN: 152062 Hom.: 41997 Cov.: 32 AF XY: 0.735 AC XY: 54611 AN XY: 74328

Gnomad4 AFR AF: 0.705

Gnomad4 AMR AF: 0.630

Gnomad4 ASJ AF: 0.732

Gnomad4 EAS AF: 0.709

Gnomad4 SAS AF: 0.689

Gnomad4 FIN AF: 0.770

Gnomad4 NFE AF: 0.788

Gnomad4 OTH AF: 0.735

Alfa AF: 0.763 Hom.: 75572

Bravo AF: 0.727

Asia WGS AF: 0.699 AC: 2436 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	-0.83
Cadd	Benign	0.063
Dann	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs12944823; hg19: chr17-12620761; COSMIC: COSV58502657; COSMIC: COSV58502657;