rs200948076
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_001039876.3(SYNE4):āc.1025A>Gā(p.Asn342Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000103 in 1,613,144 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001039876.3 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SYNE4 | NM_001039876.3 | c.1025A>G | p.Asn342Ser | missense_variant | 7/8 | ENST00000324444.9 | NP_001034965.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SYNE4 | ENST00000324444.9 | c.1025A>G | p.Asn342Ser | missense_variant | 7/8 | 5 | NM_001039876.3 | ENSP00000316130.3 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152150Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000227 AC: 56AN: 247030Hom.: 0 AF XY: 0.000283 AC XY: 38AN XY: 134080
GnomAD4 exome AF: 0.000109 AC: 159AN: 1460876Hom.: 2 Cov.: 31 AF XY: 0.000151 AC XY: 110AN XY: 726568
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152268Hom.: 0 Cov.: 31 AF XY: 0.0000940 AC XY: 7AN XY: 74462
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 18, 2016 | Variant classified as Uncertain Significance - Favor Benign. The p.Asn342Ser var iant in SYNE4 has not been previously reported in individuals with hearing loss. This variant has been identified in 0.2% (24/13354) of South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs200948076). Computational prediction tools and conservation analyses suggest that the p.Asn342Ser variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, while the clini cal significance of the p.Asn342Ser variant is uncertain, its frequency in the g eneral population suggests that it is more likely to be benign. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 04, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at