rs142791153
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The ENST00000215838.8(TCN2):c.523G>A(p.Val175Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000235 in 1,614,178 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. V175V) has been classified as Likely benign.
Frequency
Consequence
ENST00000215838.8 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TCN2 | NM_000355.4 | c.523G>A | p.Val175Met | missense_variant | 4/9 | ENST00000215838.8 | NP_000346.2 | |
TCN2 | NM_001184726.2 | c.442G>A | p.Val148Met | missense_variant | 4/9 | NP_001171655.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TCN2 | ENST00000215838.8 | c.523G>A | p.Val175Met | missense_variant | 4/9 | 1 | NM_000355.4 | ENSP00000215838 | P2 |
Frequencies
GnomAD3 genomes AF: 0.00124 AC: 189AN: 152182Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000350 AC: 88AN: 251398Hom.: 0 AF XY: 0.000221 AC XY: 30AN XY: 135892
GnomAD4 exome AF: 0.000131 AC: 191AN: 1461878Hom.: 1 Cov.: 32 AF XY: 0.000113 AC XY: 82AN XY: 727240
GnomAD4 genome AF: 0.00124 AC: 189AN: 152300Hom.: 0 Cov.: 32 AF XY: 0.00118 AC XY: 88AN XY: 74476
ClinVar
Submissions by phenotype
Transcobalamin II deficiency Uncertain:1Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jan 03, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 21, 2024 | - - |
TCN2-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 05, 2024 | This variant is classified as likely 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