1-236895448-C-T
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_000254.3(MTR):c.3496C>T(p.Leu1166Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0067 in 1,601,094 control chromosomes in the GnomAD database, including 855 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_000254.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MTR | ENST00000366577.10 | c.3496C>T | p.Leu1166Leu | synonymous_variant | Exon 31 of 33 | 1 | NM_000254.3 | ENSP00000355536.5 | ||
MTR | ENST00000366576.3 | c.2158C>T | p.Leu720Leu | synonymous_variant | Exon 18 of 20 | 1 | ENSP00000355535.3 |
Frequencies
GnomAD3 genomes AF: 0.00906 AC: 1378AN: 152168Hom.: 136 Cov.: 33
GnomAD3 exomes AF: 0.0189 AC: 4295AN: 227274Hom.: 412 AF XY: 0.0183 AC XY: 2249AN XY: 122672
GnomAD4 exome AF: 0.00646 AC: 9358AN: 1448808Hom.: 721 Cov.: 60 AF XY: 0.00659 AC XY: 4740AN XY: 719214
GnomAD4 genome AF: 0.00901 AC: 1372AN: 152286Hom.: 134 Cov.: 33 AF XY: 0.00991 AC XY: 738AN XY: 74440
ClinVar
Submissions by phenotype
not specified Benign:1
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. -
Methylcobalamin deficiency type cblG Benign:1
- -
Disorders of Intracellular Cobalamin Metabolism Benign:1
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. -
not provided Benign:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at