rs1532268
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_002454.3(MTRR):c.524C>T(p.Ser175Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 1,613,402 control chromosomes in the GnomAD database, including 100,433 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S175S) has been classified as Likely benign.
Frequency
Consequence
NM_002454.3 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 |
---|---|---|---|---|---|---|---|
MTRR | NM_002454.3 | c.524C>T | p.Ser175Leu | missense_variant | 5/15 | ENST00000440940.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MTRR | ENST00000440940.7 | c.524C>T | p.Ser175Leu | missense_variant | 5/15 | 1 | NM_002454.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.316 AC: 47805AN: 151460Hom.: 7871 Cov.: 30
GnomAD3 exomes AF: 0.311 AC: 78080AN: 251244Hom.: 13129 AF XY: 0.320 AC XY: 43445AN XY: 135790
GnomAD4 exome AF: 0.351 AC: 512993AN: 1461824Hom.: 92545 Cov.: 61 AF XY: 0.353 AC XY: 256369AN XY: 727202
GnomAD4 genome ? AF: 0.316 AC: 47854AN: 151578Hom.: 7888 Cov.: 30 AF XY: 0.313 AC XY: 23148AN XY: 74012
ClinVar
Submissions by phenotype
Methylcobalamin deficiency type cblE Benign:4
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Pars Genome Lab | Jun 19, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
not specified Benign:3
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 26, 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. - |
Gastrointestinal stromal tumor Uncertain:1
Uncertain significance, no assertion criteria provided | case-control | Department of Pharmacy and Biotechnology, University of Bologna | - | - - |
Disorders of Intracellular Cobalamin Metabolism Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Mar 06, 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