rs387906585

Variant names:

• chr15-34793467-TGATACCATGCTCGATGG-T
• rs387906585
• NM_005159.5:c.215_231delCCATCGAGCATGGTATC

Variant summary

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

The NM_005159.5(ACTC1):​c.215_231delCCATCGAGCATGGTATC​(p.Pro72HisfsTer18) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as no classifications from unflagged records (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACTC1 NM_005159.5 frameshift
• Clinical Significance: no classifications from unflagged records no classifications from unflagged records P:1
• Conservation: PhyloP100: 10.0
• Publications: 3 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 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACTC1	NM_005159.5	c.215_231delCCATCGAGCATGGTATC	p.Pro72HisfsTer18	frameshift_variant	Exon 3 of 7	ENST00000290378.6	NP_005150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACTC1	ENST00000290378.6	c.215_231delCCATCGAGCATGGTATC	p.Pro72HisfsTer18	frameshift_variant	Exon 3 of 7	1	NM_005159.5	ENSP00000290378.4

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: no classifications from unflagged records

Submissions summary: Pathogenic:1

Revision: no classifications from unflagged records

Submissions by phenotype

Atrial septal defect 5 Pathogenic:1

Jan 15, 2008

OMIM

Significance: Pathogenic

Review Status: flagged submission

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		10
Mutation Taster		=8/192	disease causing (ClinVar)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs387906585; hg19: chr15-35085668;