4-102632064-A-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_005908.4(MANBA):āc.2633T>Cā(p.Ile878Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000345 in 1,595,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_005908.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MANBA | NM_005908.4 | c.2633T>C | p.Ile878Thr | missense_variant | 17/17 | ENST00000647097.2 | NP_005899.3 | |
MANBA | XM_047415692.1 | c.2558T>C | p.Ile853Thr | missense_variant | 18/18 | XP_047271648.1 | ||
MANBA | XM_047415693.1 | c.2558T>C | p.Ile853Thr | missense_variant | 18/18 | XP_047271649.1 | ||
MANBA | XM_047415694.1 | c.1985T>C | p.Ile662Thr | missense_variant | 13/13 | XP_047271650.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MANBA | ENST00000647097.2 | c.2633T>C | p.Ile878Thr | missense_variant | 17/17 | NM_005908.4 | ENSP00000495247.1 |
Frequencies
GnomAD3 genomes AF: 0.000158 AC: 24AN: 152196Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251380Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135868
GnomAD4 exome AF: 0.0000215 AC: 31AN: 1443640Hom.: 0 Cov.: 32 AF XY: 0.0000236 AC XY: 17AN XY: 719220
GnomAD4 genome AF: 0.000158 AC: 24AN: 152196Hom.: 0 Cov.: 33 AF XY: 0.000175 AC XY: 13AN XY: 74352
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 06, 2024 | The c.2633T>C (p.I878T) alteration is located in exon 17 (coding exon 17) of the MANBA gene. This alteration results from a T to C substitution at nucleotide position 2633, causing the isoleucine (I) at amino acid position 878 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Beta-D-mannosidosis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 23, 2022 | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 878 of the MANBA protein (p.Ile878Thr). This variant is present in population databases (rs145756079, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with MANBA-related conditions. ClinVar contains an entry for this variant (Variation ID: 1395651). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at