rs769875681
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001130965.3(SUN1):c.2281C>T(p.Arg761Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,614,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R761Q) has been classified as Likely benign.
Frequency
Consequence
NM_001130965.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SUN1 | NM_001130965.3 | c.2281C>T | p.Arg761Trp | missense_variant | 19/19 | ENST00000401592.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SUN1 | ENST00000401592.6 | c.2281C>T | p.Arg761Trp | missense_variant | 19/19 | 1 | NM_001130965.3 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152208Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249574Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135406
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461882Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727238
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152208Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2AN XY: 74354
ClinVar
Submissions by phenotype
Emery-Dreifuss muscular dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 21, 2022 | 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 disruptive. 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. ClinVar contains an entry for this variant (Variation ID: 570814). This variant has not been reported in the literature in individuals affected with SUN1-related conditions. This variant is present in population databases (rs769875681, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 761 of the SUN1 protein (p.Arg761Trp). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at