rs752996514
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4
The NM_206933.4(USH2A):c.9565G>T(p.Ala3189Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_206933.4 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
USH2A | NM_206933.4 | c.9565G>T | p.Ala3189Ser | missense_variant | 48/72 | ENST00000307340.8 | NP_996816.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
USH2A | ENST00000307340.8 | c.9565G>T | p.Ala3189Ser | missense_variant | 48/72 | 1 | NM_206933.4 | ENSP00000305941.3 | ||
USH2A | ENST00000674083.1 | c.9565G>T | p.Ala3189Ser | missense_variant | 48/73 | ENSP00000501296.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250430Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135322
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460212Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 726442
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | May 30, 2024 | Variant summary: USH2A c.9565G>T (p.Ala3189Ser) results in a conservative amino acid change located in the fibronectin type III domain (IPR003961) of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 250430 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.9565G>T has been reported in the literature in the compound heterozygous state in at least one individual affected with retinitis pigmentosa (e.g. Xu_2014). This report does not provide unequivocal conclusions about association of the variant with Usher Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 24938718). ClinVar contains an entry for this variant (Variation ID: 552654). Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Usher syndrome type 2A;C3151138:Retinitis pigmentosa 39 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Jun 26, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at