chr17-12734054-T-G

Position:

• chr17-12734054-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001146312.3(MYOCD):​c.416-2107T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 151,644 control chromosomes in the GnomAD database, including 15,748 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.45 (15748 hom., cov: 30)
• Consequence: MYOCD NM_001146312.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00600

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYOCD	NM_001146312.3	c.416-2107T>G		intron_variant		ENST00000425538.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYOCD	ENST00000425538.6	c.416-2107T>G		intron_variant		1	NM_001146312.3	P2
MYOCD	ENST00000343344.8	c.416-2107T>G		intron_variant		1		A2
MYOCD	ENST00000395988.1	n.336-2107T>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68279 AN: 151526 Hom.: 15725 Cov.: 30

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.410

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

GnomAD4 genome AF: 0.451 AC: 68344 AN: 151644 Hom.: 15748 Cov.: 30 AF XY: 0.454 AC XY: 33631 AN XY: 74060

Gnomad4 AFR AF: 0.516

Gnomad4 AMR AF: 0.458

Gnomad4 ASJ AF: 0.348

Gnomad4 EAS AF: 0.670

Gnomad4 SAS AF: 0.482

Gnomad4 FIN AF: 0.473

Gnomad4 NFE AF: 0.395

Gnomad4 OTH AF: 0.411

Alfa AF: 0.407 Hom.: 15489

Bravo AF: 0.455

Asia WGS AF: 0.544 AC: 1892 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.9
DANN	Benign	0.67

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: rs9905820; hg19: chr17-12637371; COSMIC: COSV58500262;