17-12722609-G-A

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.254-238G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0506 in 152,128 control chromosomes in the GnomAD database, including 305 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.051 (305 hom., cov: 32)
• Consequence: MYOCD NM_001146312.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.30

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=-0.72).
• BP6: Variant 17-12722609-G-A is Benign according to our data. Variant chr17-12722609-G-A is described in ClinVar as [Benign]. Clinvar id is 1245866.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYOCD	NM_001146312.3	c.254-238G>A		intron_variant		ENST00000425538.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYOCD	ENST00000425538.6	c.254-238G>A		intron_variant		1	NM_001146312.3	P2
MYOCD	ENST00000343344.8	c.254-238G>A		intron_variant		1		A2
MYOCD	ENST00000395988.1	n.174-238G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0505 AC: 7682 AN: 152010 Hom.: 299 Cov.: 32

Gnomad AFR AF: 0.0745

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.0306

Gnomad EAS AF: 0.0818

Gnomad SAS AF: 0.0504

Gnomad FIN AF: 0.0315

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0215

Gnomad OTH AF: 0.0435

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

GnomAD4 genome AF: 0.0506 AC: 7703 AN: 152128 Hom.: 305 Cov.: 32 AF XY: 0.0535 AC XY: 3977 AN XY: 74374

Gnomad4 AFR AF: 0.0744

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.0306

Gnomad4 EAS AF: 0.0818

Gnomad4 SAS AF: 0.0500

Gnomad4 FIN AF: 0.0315

Gnomad4 NFE AF: 0.0215

Gnomad4 OTH AF: 0.0445

Alfa AF: 0.0435 Hom.: 143

Bravo AF: 0.0604

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	14
Dann	Benign	0.77

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: rs10521200; hg19: chr17-12625926;