rs1239032275
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM2BP4_ModerateBP6_Moderate
The NM_206933.4(USH2A):āc.1942A>Gā(p.Thr648Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,613,866 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (ā ). Synonymous variant affecting the same amino acid position (i.e. T648T) has been classified as Likely benign.
Frequency
Consequence
NM_206933.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USH2A | NM_206933.4 | c.1942A>G | p.Thr648Ala | missense_variant | 11/72 | ENST00000307340.8 | |
USH2A | NM_007123.6 | c.1942A>G | p.Thr648Ala | missense_variant | 11/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USH2A | ENST00000307340.8 | c.1942A>G | p.Thr648Ala | missense_variant | 11/72 | 1 | NM_206933.4 | P1 | |
USH2A | ENST00000366942.3 | c.1942A>G | p.Thr648Ala | missense_variant | 11/21 | 1 | |||
USH2A | ENST00000674083.1 | c.1942A>G | p.Thr648Ala | missense_variant | 11/73 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152184Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461682Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727150
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74352
ClinVar
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 10, 2017 | p.Thr648Ala in exon 11 of USH2A: This variant is not expected to have clinical s ignificance due to a lack of conservation across species, including mammals. Of note, 6 mammals have an alanine (Ala) at this position. In addition, computation al prediction tools do not suggest a high likelihood of impact to the protein. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at