17-12704954-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.56-174T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0891 in 588,548 control chromosomes in the GnomAD database, including 2,632 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.092 (670 hom., cov: 32)
  • Exomes 𝑓: 0.088 (1962 hom.)
• Consequence: MYOCD NM_001146312.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.525

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]

MYOCD-AS1 (HGNC:40750): (MYOCD antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 17-12704954-T-C is Benign according to our data. Variant chr17-12704954-T-C is described in ClinVar as [Benign]. Clinvar id is 1182207.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYOCD	NM_001146312.3	c.56-174T>C		intron_variant		ENST00000425538.6
MYOCD-AS1	NR_104605.1	n.793A>G		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYOCD	ENST00000425538.6	c.56-174T>C		intron_variant		1	NM_001146312.3	P2
MYOCD	ENST00000343344.8	c.56-174T>C		intron_variant		1		A2
MYOCD-AS1	ENST00000445508.1	n.793A>G		non_coding_transcript_exon_variant	2/3	1
MYOCD	ENST00000579237.5	c.56-174T>C		intron_variant, NMD_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0918 AC: 13974 AN: 152164 Hom.: 669 Cov.: 32

Gnomad AFR AF: 0.0895

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.0723

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.0196

Gnomad SAS AF: 0.0515

Gnomad FIN AF: 0.0804

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0929

GnomAD4 exome AF: 0.0882 AC: 38478 AN: 436266 Hom.: 1962 Cov.: 4 AF XY: 0.0864 AC XY: 19883 AN XY: 230064

Gnomad4 AFR exome AF: 0.0835

Gnomad4 AMR exome AF: 0.0656

Gnomad4 ASJ exome AF: 0.107

Gnomad4 EAS exome AF: 0.0166

Gnomad4 SAS exome AF: 0.0483

Gnomad4 FIN exome AF: 0.0802

Gnomad4 NFE exome AF: 0.105

Gnomad4 OTH exome AF: 0.0847

GnomAD4 genome AF: 0.0918 AC: 13979 AN: 152282 Hom.: 670 Cov.: 32 AF XY: 0.0880 AC XY: 6553 AN XY: 74468

Gnomad4 AFR AF: 0.0894

Gnomad4 AMR AF: 0.0721

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.0195

Gnomad4 SAS AF: 0.0518

Gnomad4 FIN AF: 0.0804

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.0919

Alfa AF: 0.0990 Hom.: 219

Bravo AF: 0.0917

Asia WGS AF: 0.0320 AC: 114 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

Jun 20, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	9.0
Dann	Benign	0.48

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: rs8073609; hg19: chr17-12608271;