chrX-74740782-C-T
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_001008537.3(NEXMIF):c.3775G>A(p.Ala1259Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000297 in 1,210,553 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1259D) 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 -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEXMIF | NM_001008537.3 | c.3775G>A | p.Ala1259Thr | missense_variant | 3/4 | ENST00000055682.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEXMIF | ENST00000055682.12 | c.3775G>A | p.Ala1259Thr | missense_variant | 3/4 | 1 | NM_001008537.3 | P1 | |
NEXMIF | ENST00000616200.2 | c.3775G>A | p.Ala1259Thr | missense_variant | 3/5 | 1 | P1 | ||
NEXMIF | ENST00000642681.2 | c.3775G>A | p.Ala1259Thr | missense_variant | 3/3 |
Frequencies
GnomAD3 genomes ? AF: 0.000213 AC: 24AN: 112801Hom.: 0 Cov.: 23 AF XY: 0.000258 AC XY: 9AN XY: 34941
GnomAD3 exomes AF: 0.00000548 AC: 1AN: 182355Hom.: 0 AF XY: 0.0000149 AC XY: 1AN XY: 67017
GnomAD4 exome AF: 0.0000109 AC: 12AN: 1097752Hom.: 0 Cov.: 32 AF XY: 0.00000826 AC XY: 3AN XY: 363148
GnomAD4 genome ? AF: 0.000213 AC: 24AN: 112801Hom.: 0 Cov.: 23 AF XY: 0.000258 AC XY: 9AN XY: 34941
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 31, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 09, 2020 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 15, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at