NM_005908.4:c.757G>A
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_005908.4(MANBA):c.757G>A(p.Val253Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 1,608,542 control chromosomes in the GnomAD database, including 177,288 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 Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V253L) has been classified as Likely benign.
Frequency
Consequence
NM_005908.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MANBA | NM_005908.4 | c.757G>A | p.Val253Ile | missense_variant | Exon 6 of 17 | ENST00000647097.2 | NP_005899.3 | |
MANBA | XM_047415692.1 | c.682G>A | p.Val228Ile | missense_variant | Exon 7 of 18 | XP_047271648.1 | ||
MANBA | XM_047415693.1 | c.682G>A | p.Val228Ile | missense_variant | Exon 7 of 18 | XP_047271649.1 | ||
MANBA | XM_047415694.1 | c.109G>A | p.Val37Ile | missense_variant | Exon 2 of 13 | XP_047271650.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.397 AC: 60244AN: 151564Hom.: 13440 Cov.: 30
GnomAD3 exomes AF: 0.442 AC: 110738AN: 250716Hom.: 25805 AF XY: 0.453 AC XY: 61456AN XY: 135530
GnomAD4 exome AF: 0.469 AC: 683469AN: 1456860Hom.: 163837 Cov.: 33 AF XY: 0.471 AC XY: 341743AN XY: 724962
GnomAD4 genome AF: 0.397 AC: 60267AN: 151682Hom.: 13451 Cov.: 30 AF XY: 0.399 AC XY: 29595AN XY: 74092
ClinVar
Submissions by phenotype
not provided Benign:3
- -
- -
- -
Beta-D-mannosidosis Benign:3
- -
- -
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 specified Benign:2
- -
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at