rs193920964

Variant names:

• chr17-12763359-GA-G
• rs193920964
• NM_001146312.3:c.2678delA

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PVS1_Moderate PM2

The NM_001146312.3(MYOCD):​c.2678delA​(p.Lys893ArgfsTer36) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYOCD NM_001146312.3 frameshift
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 5.17
• Publications: 0 publications found

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]

ARHGAP44-AS1 (HGNC:55326): (ARHGAP44 and MYOCD antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0956 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146312.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOCD	NM_001146312.3	MANE Select	c.2678delA	p.Lys893ArgfsTer36	frameshift	Exon 14 of 14	NP_001139784.1	Q8IZQ8-3
	MYOCD	NM_153604.4		c.2534delA	p.Lys845ArgfsTer36	frameshift	Exon 13 of 13	NP_705832.1	Q8IZQ8-1
	MYOCD	NM_001378306.1		c.2441delA	p.Lys814ArgfsTer36	frameshift	Exon 15 of 15	NP_001365235.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOCD	ENST00000425538.6	TSL:1 MANE Select	c.2678delA	p.Lys893ArgfsTer36	frameshift	Exon 14 of 14	ENSP00000401678.1	Q8IZQ8-3
	MYOCD	ENST00000343344.8	TSL:1	c.2534delA	p.Lys845ArgfsTer36	frameshift	Exon 13 of 13	ENSP00000341835.4	Q8IZQ8-1
	MYOCD	ENST00000443061.1	TSL:1	c.1664delA	p.Lys555ArgfsTer36	frameshift	Exon 6 of 6	ENSP00000400148.2	Q6N065

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs193920964;

hg19: chr17-12666676;

COSMIC: COSV58508083;