17-12744091-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.718-92A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0461 in 1,452,046 control chromosomes in the GnomAD database, including 1,693 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.058 (303 hom., cov: 31)
  • Exomes 𝑓: 0.045 (1390 hom.)
• Consequence: MYOCD NM_001146312.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.226

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=-0.74).
• BP6: Variant 17-12744091-A-G is Benign according to our data. Variant chr17-12744091-A-G is described in ClinVar as [Benign]. Clinvar id is 1221524.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYOCD	NM_001146312.3	c.718-92A>G		intron_variant		ENST00000425538.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYOCD	ENST00000425538.6	c.718-92A>G		intron_variant		1	NM_001146312.3	P2
MYOCD	ENST00000343344.8	c.718-92A>G		intron_variant		1		A2
MYOCD	ENST00000395988.1	n.638-92A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0580 AC: 8824 AN: 152114 Hom.: 303 Cov.: 31

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.0433

Gnomad ASJ AF: 0.0657

Gnomad EAS AF: 0.0291

Gnomad SAS AF: 0.0560

Gnomad FIN AF: 0.0232

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0399

Gnomad OTH AF: 0.0484

GnomAD4 exome AF: 0.0447 AC: 58090 AN: 1299814 Hom.: 1390 AF XY: 0.0447 AC XY: 28783 AN XY: 643534

Gnomad4 AFR exome AF: 0.107

Gnomad4 AMR exome AF: 0.0364

Gnomad4 ASJ exome AF: 0.0638

Gnomad4 EAS exome AF: 0.0275

Gnomad4 SAS exome AF: 0.0560

Gnomad4 FIN exome AF: 0.0206

Gnomad4 NFE exome AF: 0.0437

Gnomad4 OTH exome AF: 0.0481

GnomAD4 genome AF: 0.0580 AC: 8833 AN: 152232 Hom.: 303 Cov.: 31 AF XY: 0.0569 AC XY: 4235 AN XY: 74434

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.0433

Gnomad4 ASJ AF: 0.0657

Gnomad4 EAS AF: 0.0292

Gnomad4 SAS AF: 0.0563

Gnomad4 FIN AF: 0.0232

Gnomad4 NFE AF: 0.0399

Gnomad4 OTH AF: 0.0493

Alfa AF: 0.0483 Hom.: 156

Bravo AF: 0.0608

Asia WGS AF: 0.0550 AC: 191 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 21, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	0.64
Dann	Benign	0.74

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: rs8073291; hg19: chr17-12647408;