X-74739491-C-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001008537.3(NEXMIF):c.4465G>A(p.Asp1489Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,074,334 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. D1489D) has been classified as Likely benign.
Frequency
Consequence
NM_001008537.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEXMIF | NM_001008537.3 | c.4465G>A | p.Asp1489Asn | missense_variant | 4/4 | ENST00000055682.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEXMIF | ENST00000055682.12 | c.4465G>A | p.Asp1489Asn | missense_variant | 4/4 | 1 | NM_001008537.3 | P1 | |
NEXMIF | ENST00000616200.2 | c.4465G>A | p.Asp1489Asn | missense_variant | 4/5 | 1 | P1 | ||
NEXMIF | ENST00000642681.2 | c.*605G>A | 3_prime_UTR_variant | 3/3 |
Frequencies
GnomAD3 genomes Cov.: 21
GnomAD3 exomes AF: 0.0000121 AC: 2AN: 165637Hom.: 0 AF XY: 0.0000189 AC XY: 1AN XY: 52933
GnomAD4 exome AF: 0.00000558 AC: 6AN: 1074334Hom.: 0 Cov.: 25 AF XY: 0.00000585 AC XY: 2AN XY: 341816
GnomAD4 genome Cov.: 21
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 28, 2020 | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Mar 08, 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 asparagine 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: 1313198). This variant has not been reported in the literature in individuals affected with NEXMIF-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1489 of the NEXMIF protein (p.Asp1489Asn). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at