rs2229464
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The ENST00000206765.11(TGM1):c.1819C>T(p.Arg607Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000768 in 1,614,146 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R607H) has been classified as Likely benign.
Frequency
Consequence
ENST00000206765.11 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TGM1 | NM_000359.3 | c.1819C>T | p.Arg607Cys | missense_variant | 12/15 | ENST00000206765.11 | NP_000350.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TGM1 | ENST00000206765.11 | c.1819C>T | p.Arg607Cys | missense_variant | 12/15 | 1 | NM_000359.3 | ENSP00000206765 | P1 | |
TGM1 | ENST00000544573.5 | c.493C>T | p.Arg165Cys | missense_variant | 6/9 | 2 | ENSP00000439446 | |||
TGM1 | ENST00000559669.1 | upstream_gene_variant | 3 | ENSP00000453701 |
Frequencies
GnomAD3 genomes AF: 0.00392 AC: 597AN: 152194Hom.: 7 Cov.: 33
GnomAD3 exomes AF: 0.00109 AC: 274AN: 251364Hom.: 0 AF XY: 0.000758 AC XY: 103AN XY: 135888
GnomAD4 exome AF: 0.000438 AC: 640AN: 1461834Hom.: 6 Cov.: 34 AF XY: 0.000393 AC XY: 286AN XY: 727216
GnomAD4 genome AF: 0.00393 AC: 599AN: 152312Hom.: 7 Cov.: 33 AF XY: 0.00388 AC XY: 289AN XY: 74478
ClinVar
Submissions by phenotype
Autosomal recessive congenital ichthyosis 1 Benign:3
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Apr 17, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Oct 29, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | - | - - |
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2024 | TGM1: BP4, BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
TGM1-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 27, 2020 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at