chr15-34793512-TG-T

Variant names:

• chr15-34793512-TG-T
• rs876657739
• NM_005159.5:c.186delC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005159.5(ACTC1):​c.186delC​(p.Ser62ArgfsTer6) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACTC1 NM_005159.5 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.92
• Publications: 0 publications found

Genes affected

ACTC1 (HGNC:143): (actin alpha cardiac muscle 1) Actins are highly conserved proteins that are involved in various types of cell motility. Polymerization of globular actin (G-actin) leads to a structural filament (F-actin) in the form of a two-stranded helix. Each actin can bind to four others. The protein encoded by this gene belongs to the actin family which is comprised of three main groups of actin isoforms, alpha, beta, and gamma. The alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. Defects in this gene have been associated with idiopathic dilated cardiomyopathy (IDC) and familial hypertrophic cardiomyopathy (FHC). [provided by RefSeq, Jul 2008]

GJD2-DT (HGNC:55560): (GJD2 divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005159.5. 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
	ACTC1	NM_005159.5	MANE Select	c.186delC	p.Ser62ArgfsTer6	frameshift	Exon 3 of 7	NP_005150.1	P68032
	ACTC1	NM_001406482.1		c.186delC	p.Ser62ArgfsTer6	frameshift	Exon 2 of 6	NP_001393411.1	P68032
	ACTC1	NM_001406483.1		c.186delC	p.Ser62ArgfsTer6	frameshift	Exon 3 of 7	NP_001393412.1	P68032

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTC1	ENST00000290378.6	TSL:1 MANE Select	c.186delC	p.Ser62ArgfsTer6	frameshift	Exon 3 of 7	ENSP00000290378.4	P68032
	ACTC1	ENST00000713613.1		c.297delC	p.Ser99ArgfsTer6	frameshift	Exon 4 of 8	ENSP00000518909.1	A0AAQ5BGG2
	ACTC1	ENST00000868408.1		c.186delC	p.Ser62ArgfsTer6	frameshift	Exon 3 of 7	ENSP00000538467.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.9

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

Other links and lift over

dbSNP: rs876657739; hg19: chr15-35085713;