rs201804636
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001130965.3(SUN1):c.1732G>A(p.Val578Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,614,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001130965.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152236Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000161 AC: 4AN: 248556Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 134976
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461858Hom.: 0 Cov.: 33 AF XY: 0.0000124 AC XY: 9AN XY: 727232
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152236Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74382
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.1732G>A (p.V578M) alteration is located in exon 14 (coding exon 14) of the SUN1 gene. This alteration results from a G to A substitution at nucleotide position 1732, causing the valine (V) at amino acid position 578 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Emery-Dreifuss muscular dystrophy Uncertain:1
This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 578 of the SUN1 protein (p.Val578Met). This variant is present in population databases (rs201804636, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with SUN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1059215). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at