rs186535459
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_001008537.3(NEXMIF):āc.2672A>Gā(p.Asn891Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000859 in 1,210,456 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 24 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). Synonymous variant affecting the same amino acid position (i.e. N891N) 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.2672A>G | p.Asn891Ser | missense_variant | 3/4 | ENST00000055682.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEXMIF | ENST00000055682.12 | c.2672A>G | p.Asn891Ser | missense_variant | 3/4 | 1 | NM_001008537.3 | P1 | |
NEXMIF | ENST00000616200.2 | c.2672A>G | p.Asn891Ser | missense_variant | 3/5 | 1 | P1 | ||
NEXMIF | ENST00000642681.2 | c.2672A>G | p.Asn891Ser | missense_variant | 3/3 |
Frequencies
GnomAD3 genomes AF: 0.0000801 AC: 9AN: 112335Hom.: 0 Cov.: 22 AF XY: 0.0000290 AC XY: 1AN XY: 34505
GnomAD3 exomes AF: 0.000448 AC: 82AN: 183202Hom.: 0 AF XY: 0.000251 AC XY: 17AN XY: 67714
GnomAD4 exome AF: 0.0000856 AC: 94AN: 1098065Hom.: 0 Cov.: 32 AF XY: 0.0000633 AC XY: 23AN XY: 363435
GnomAD4 genome AF: 0.0000890 AC: 10AN: 112391Hom.: 0 Cov.: 22 AF XY: 0.0000289 AC XY: 1AN XY: 34571
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 13, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 08, 2021 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 28, 2017 | This alteration is classified as 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. - |
NEXMIF-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 18, 2024 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at