NM_182914.3:c.4738G>T
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2
The NM_182914.3(SYNE2):c.4738G>T(p.Val1580Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000517 in 1,584,938 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 Uncertain significance (★).
Frequency
Consequence
NM_182914.3 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SYNE2 | NM_182914.3 | c.4738G>T | p.Val1580Phe | missense_variant | Exon 33 of 116 | ENST00000555002.6 | NP_878918.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SYNE2 | ENST00000555002.6 | c.4738G>T | p.Val1580Phe | missense_variant | Exon 33 of 116 | 1 | NM_182914.3 | ENSP00000450831.2 |
Frequencies
GnomAD3 genomes AF: 0.000289 AC: 44AN: 152082Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000731 AC: 17AN: 232676Hom.: 0 AF XY: 0.0000476 AC XY: 6AN XY: 125932
GnomAD4 exome AF: 0.0000265 AC: 38AN: 1432738Hom.: 0 Cov.: 27 AF XY: 0.0000253 AC XY: 18AN XY: 712322
GnomAD4 genome AF: 0.000289 AC: 44AN: 152200Hom.: 0 Cov.: 31 AF XY: 0.000376 AC XY: 28AN XY: 74404
ClinVar
Submissions by phenotype
Emery-Dreifuss muscular dystrophy 5, autosomal dominant Uncertain:1
This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 1580 of the SYNE2 protein (p.Val1580Phe). This variant is present in population databases (rs190340029, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with SYNE2-related conditions. ClinVar contains an entry for this variant (Variation ID: 470974). 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 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at