rs199917913
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_144573.4(NEXN):c.856C>T(p.Arg286Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000799 in 1,613,526 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R286Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_144573.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEXN | NM_144573.4 | c.856C>T | p.Arg286Trp | missense_variant | 8/13 | ENST00000334785.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEXN | ENST00000334785.12 | c.856C>T | p.Arg286Trp | missense_variant | 8/13 | 1 | NM_144573.4 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000921 AC: 14AN: 151940Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000133 AC: 33AN: 247848Hom.: 0 AF XY: 0.000119 AC XY: 16AN XY: 134794
GnomAD4 exome AF: 0.0000787 AC: 115AN: 1461586Hom.: 0 Cov.: 32 AF XY: 0.0000811 AC XY: 59AN XY: 727080
GnomAD4 genome ? AF: 0.0000921 AC: 14AN: 151940Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2AN XY: 74188
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 29, 2020 | Reported in an individual with left ventricular hypertrabeculation, although no additional clinical or segregation data were provided (Miszalski-Jamka et al., 2017); Reported in ClinVar as a variant of uncertain significance or likely benign variant by other clinical laboratories (ClinVar Variant ID# 201919; Landrum et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28798025) - |
Primary familial hypertrophic cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute | Aug 31, 2016 | - - |
Cardiomyopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Sep 14, 2018 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 29, 2018 | 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. - |
Dilated cardiomyopathy 1CC;C3151267:Hypertrophic cardiomyopathy 20 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 01, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at