chr14-24249311-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000359.3(TGM1):c.*2C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,612,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
TGM1
NM_000359.3 3_prime_UTR
NM_000359.3 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.47
Genes affected
TGM1 (HGNC:11777): (transglutaminase 1) The protein encoded by this gene is a membrane protein that catalyzes the addition of an alkyl group from an akylamine to a glutamine residue of a protein, forming an alkylglutamine in the protein. This protein alkylation leads to crosslinking of proteins and catenation of polyamines to proteins. This gene contains either one or two copies of a 22 nt repeat unit in its 3' UTR. Mutations in this gene have been associated with autosomal recessive lamellar ichthyosis (LI) and nonbullous congenital ichthyosiform erythroderma (NCIE). [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TGM1 | NM_000359.3 | c.*2C>T | 3_prime_UTR_variant | 15/15 | ENST00000206765.11 | NP_000350.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TGM1 | ENST00000206765.11 | c.*2C>T | 3_prime_UTR_variant | 15/15 | 1 | NM_000359.3 | ENSP00000206765 | P1 | ||
TGM1 | ENST00000544573.5 | c.*2C>T | 3_prime_UTR_variant | 9/9 | 2 | ENSP00000439446 |
Frequencies
GnomAD3 genomes AF: 0.0000395 AC: 6AN: 151986Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250462Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135430
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GnomAD4 exome AF: 0.00000411 AC: 6AN: 1460572Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1AN XY: 726608
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GnomAD4 genome AF: 0.0000395 AC: 6AN: 151986Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74222
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Autosomal recessive congenital ichthyosis 1 Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Apr 17, 2020 | - - |
Computational scores
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Benign
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DANN
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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