chr16-2039931-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_002528.7(NTHL1):c.908G>A(p.Gly303Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G303R) has been classified as Likely benign.
Frequency
Consequence
NM_002528.7 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 | UniProt |
---|---|---|---|---|---|---|---|
NTHL1 | NM_002528.7 | c.908G>A | p.Gly303Asp | missense_variant | 6/6 | ENST00000651570.2 | |
NTHL1 | NM_001318193.2 | c.737G>A | p.Gly246Asp | missense_variant | 5/5 | ||
NTHL1 | NM_001318194.2 | c.578G>A | p.Gly193Asp | missense_variant | 6/6 | ||
NTHL1 | XM_047434171.1 | c.629G>A | p.Gly210Asp | missense_variant | 6/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NTHL1 | ENST00000651570.2 | c.908G>A | p.Gly303Asp | missense_variant | 6/6 | NM_002528.7 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1450092Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 721672
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 24, 2023 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The aspartic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 1474532). This variant has not been reported in the literature in individuals affected with NTHL1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine with aspartic acid at codon 311 of the NTHL1 protein (p.Gly311Asp). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.