chr15-43234829-ACTGC-TGAAGGA

Position:

• chr15-43234829-ACTGC-TGAAGGA

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_201631.4(TGM5):​c.1811_1815delinsTCCTTCA​(p.Ser604IlefsTer9) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TGM5 NM_201631.4 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 1.84

Genes affected

TGM5 (HGNC:11781): (transglutaminase 5) This gene encodes a member of the transglutaminase family. The encoded protein catalyzes formation of protein cross-links between glutamine and lysine residues, often resulting in stabilization of protein assemblies. This reaction is calcium dependent. Mutations in this gene have been associated with acral peeling skin syndrome. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 15-43234829-ACTGC-TGAAGGA is Pathogenic according to our data. Variant chr15-43234829-ACTGC-TGAAGGA is described in ClinVar as [Pathogenic]. Clinvar id is 157571.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGM5	NM_201631.4	c.1811_1815delinsTCCTTCA	p.Ser604IlefsTer9	frameshift_variant	11/13	ENST00000220420.10
TGM5	NM_004245.4	c.1565_1569delinsTCCTTCA	p.Ser522IlefsTer9	frameshift_variant	10/12
TGM5	XM_011522230.3	c.782_786delinsTCCTTCA	p.Ser261IlefsTer9	frameshift_variant	5/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGM5	ENST00000220420.10	c.1811_1815delinsTCCTTCA	p.Ser604IlefsTer9	frameshift_variant	11/13	1	NM_201631.4	P1
TGM5	ENST00000349114.8	c.1565_1569delinsTCCTTCA	p.Ser522IlefsTer9	frameshift_variant	10/12	1
TGM5	ENST00000396996.3	n.1287_1291delinsTCCTTCA		non_coding_transcript_exon_variant	4/6	2

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: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Acral peeling skin syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Oct 01, 2012

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs606231278; hg19: chr15-43527027;