rs606231277
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_201631.4(TGM5):c.640del(p.Leu214CysfsTer15) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000212 in 1,461,430 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000021 ( 0 hom. )
Consequence
TGM5
NM_201631.4 frameshift
NM_201631.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.716
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 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 15-43253549-AG-A is Pathogenic according to our data. Variant chr15-43253549-AG-A is described in ClinVar as [Pathogenic]. Clinvar id is 157570.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TGM5 | NM_201631.4 | c.640del | p.Leu214CysfsTer15 | frameshift_variant | 5/13 | ENST00000220420.10 | |
TGM5 | NM_004245.4 | c.394del | p.Leu132CysfsTer15 | frameshift_variant | 4/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TGM5 | ENST00000220420.10 | c.640del | p.Leu214CysfsTer15 | frameshift_variant | 5/13 | 1 | NM_201631.4 | P1 | |
TGM5 | ENST00000349114.8 | c.394del | p.Leu132CysfsTer15 | frameshift_variant | 4/12 | 1 | |||
TGM5 | ENST00000635871.1 | n.109del | non_coding_transcript_exon_variant | 1/4 | 4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251256Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135828
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GnomAD4 exome AF: 0.0000212 AC: 31AN: 1461430Hom.: 0 Cov.: 33 AF XY: 0.0000220 AC XY: 16AN XY: 727056
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GnomAD4 genome ? Cov.: 32
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Peeling skin syndrome 1 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Acral peeling skin syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 01, 2012 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at