rs762983389
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001008537.3(NEXMIF):āc.2504A>Cā(p.His835Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000127 in 1,098,098 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 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 (ā ā ).
Frequency
Consequence
NM_001008537.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NEXMIF | NM_001008537.3 | c.2504A>C | p.His835Pro | missense_variant | 3/4 | ENST00000055682.12 | NP_001008537.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NEXMIF | ENST00000055682.12 | c.2504A>C | p.His835Pro | missense_variant | 3/4 | 1 | NM_001008537.3 | ENSP00000055682.5 | ||
NEXMIF | ENST00000616200.2 | c.2504A>C | p.His835Pro | missense_variant | 3/5 | 1 | ENSP00000480284.1 | |||
NEXMIF | ENST00000642681.2 | c.2504A>C | p.His835Pro | missense_variant | 3/3 | ENSP00000495800.1 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 1AN: 112012Hom.: 0 Cov.: 23 AF XY: 0.0000293 AC XY: 1AN XY: 34180 FAILED QC
GnomAD3 exomes AF: 0.0000273 AC: 5AN: 183251Hom.: 0 AF XY: 0.0000148 AC XY: 1AN XY: 67763
GnomAD4 exome AF: 0.0000127 AC: 14AN: 1098098Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 5AN XY: 363464
GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000893 AC: 1AN: 112012Hom.: 0 Cov.: 23 AF XY: 0.0000293 AC XY: 1AN XY: 34180
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 25, 2019 | 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 18, 2022 | This sequence change replaces histidine, which is basic and polar, with proline, which is neutral and non-polar, at codon 835 of the NEXMIF protein (p.His835Pro). This variant is present in population databases (rs762983389, gnomAD 0.01%). 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 541120). This variant has not been reported in the literature in individuals affected with NEXMIF-related conditions. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at