rs33955793
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_025265.4(TSEN2):c.377G>A(p.Arg126His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0675 in 1,614,116 control chromosomes in the GnomAD database, including 5,414 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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. R126C) has been classified as Likely benign.
Frequency
Consequence
NM_025265.4 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 | UniProt |
---|---|---|---|---|---|---|---|
TSEN2 | NM_025265.4 | c.377G>A | p.Arg126His | missense_variant | 5/12 | ENST00000284995.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSEN2 | ENST00000284995.11 | c.377G>A | p.Arg126His | missense_variant | 5/12 | 1 | NM_025265.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0720 AC: 10957AN: 152128Hom.: 522 Cov.: 32
GnomAD3 exomes AF: 0.0873 AC: 21940AN: 251324Hom.: 2142 AF XY: 0.0773 AC XY: 10504AN XY: 135834
GnomAD4 exome AF: 0.0670 AC: 97900AN: 1461870Hom.: 4890 Cov.: 32 AF XY: 0.0644 AC XY: 46830AN XY: 727234
GnomAD4 genome ? AF: 0.0721 AC: 10973AN: 152246Hom.: 524 Cov.: 32 AF XY: 0.0728 AC XY: 5421AN XY: 74444
ClinVar
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 30, 2013 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 09, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Pontoneocerebellar hypoplasia Benign:1
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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at