chr14-24249373-G-A
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_000359.3(TGM1):c.2394C>T(p.Asp798=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000103 in 1,614,008 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00010 ( 0 hom. )
Consequence
TGM1
NM_000359.3 synonymous
NM_000359.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.21
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 Likely_benign. Variant got -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BP6
Variant 14-24249373-G-A is Benign according to our data. Variant chr14-24249373-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 991478.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-2.21 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TGM1 | NM_000359.3 | c.2394C>T | p.Asp798= | synonymous_variant | 15/15 | ENST00000206765.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TGM1 | ENST00000206765.11 | c.2394C>T | p.Asp798= | synonymous_variant | 15/15 | 1 | NM_000359.3 | P1 | |
TGM1 | ENST00000544573.5 | c.1068C>T | p.Asp356= | synonymous_variant | 9/9 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000138 AC: 21AN: 152078Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000322 AC: 81AN: 251304Hom.: 0 AF XY: 0.000243 AC XY: 33AN XY: 135852
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GnomAD4 exome AF: 0.0000999 AC: 146AN: 1461812Hom.: 0 Cov.: 34 AF XY: 0.0000866 AC XY: 63AN XY: 727204
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GnomAD4 genome AF: 0.000138 AC: 21AN: 152196Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74408
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ClinVar
Significance: Likely benign
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, single submitter
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 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
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Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at