chrX-74739496-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001008537.3(NEXMIF):c.4460A>G(p.Asp1487Gly) variant causes a missense, splice region 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. 13/19 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001008537.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NEXMIF | NM_001008537.3 | c.4460A>G | p.Asp1487Gly | missense_variant, splice_region_variant | 4/4 | ENST00000055682.12 | NP_001008537.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NEXMIF | ENST00000055682.12 | c.4460A>G | p.Asp1487Gly | missense_variant, splice_region_variant | 4/4 | 1 | NM_001008537.3 | ENSP00000055682 | P1 | |
NEXMIF | ENST00000616200.2 | c.4460A>G | p.Asp1487Gly | missense_variant, splice_region_variant | 4/5 | 1 | ENSP00000480284 | P1 | ||
NEXMIF | ENST00000642681.2 | c.*600A>G | 3_prime_UTR_variant | 3/3 | ENSP00000495800 |
Frequencies
GnomAD3 genomes Cov.: 21
GnomAD4 exome Cov.: 24
GnomAD4 genome Cov.: 21
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Apr 08, 2019 | This sequence change replaces aspartic acid with glycine at codon 1487 of the NEXMIF protein (p.Asp1487Gly). The aspartic acid residue is moderately conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NEXMIF-related conditions. 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 glycine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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