17-74920412-C-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_173477.5(USH1G):c.424G>A(p.Glu142Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00691 in 1,613,462 control chromosomes in the GnomAD database, including 604 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_173477.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
USH1G | NM_173477.5 | c.424G>A | p.Glu142Lys | missense_variant | Exon 2 of 3 | ENST00000614341.5 | NP_775748.2 | |
USH1G | NM_001282489.3 | c.115G>A | p.Glu39Lys | missense_variant | Exon 2 of 3 | NP_001269418.1 | ||
USH1G | XM_011524296.2 | c.115G>A | p.Glu39Lys | missense_variant | Exon 2 of 3 | XP_011522598.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
USH1G | ENST00000614341.5 | c.424G>A | p.Glu142Lys | missense_variant | Exon 2 of 3 | 1 | NM_173477.5 | ENSP00000480279.1 | ||
USH1G | ENST00000579243.1 | n.*23G>A | non_coding_transcript_exon_variant | Exon 2 of 3 | 2 | ENSP00000462568.1 | ||||
USH1G | ENST00000579243.1 | n.*23G>A | 3_prime_UTR_variant | Exon 2 of 3 | 2 | ENSP00000462568.1 |
Frequencies
GnomAD3 genomes AF: 0.0362 AC: 5515AN: 152222Hom.: 299 Cov.: 33
GnomAD3 exomes AF: 0.00992 AC: 2481AN: 250192Hom.: 145 AF XY: 0.00730 AC XY: 989AN XY: 135556
GnomAD4 exome AF: 0.00385 AC: 5629AN: 1461122Hom.: 304 Cov.: 42 AF XY: 0.00339 AC XY: 2466AN XY: 726894
GnomAD4 genome AF: 0.0362 AC: 5521AN: 152340Hom.: 300 Cov.: 33 AF XY: 0.0354 AC XY: 2635AN XY: 74496
ClinVar
Submissions by phenotype
not provided Benign:3
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not specified Benign:2
Glu142Lys in exon 2 of USH1G: This variant is not expected to have clinical sign ificance because it has been identified in 5.9% (300/5015) of a broad population (dbSNP rs111033466). -
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Usher syndrome type 1G Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at