rs569032124
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6BP7BS1
The NM_173477.5(USH1G):c.1152C>T(p.Asp384=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,612,862 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00012 ( 0 hom. )
Consequence
USH1G
NM_173477.5 synonymous
NM_173477.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.00
Genes affected
USH1G (HGNC:16356): (USH1 protein network component sans) This gene encodes a protein that contains three ankyrin domains, a class I PDZ-binding motif and a sterile alpha motif. The encoded protein interacts with harmonin, which is associated with Usher syndrome type 1C. This protein plays a role in the development and maintenance of the auditory and visual systems and functions in the cohesion of hair bundles formed by inner ear sensory cells. Mutations in this gene are associated with Usher syndrome type 1G (USH1G). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
Variant 17-74919684-G-A is Benign according to our data. Variant chr17-74919684-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 178968.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=2}. Variant chr17-74919684-G-A is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=1 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0000788 (12/152340) while in subpopulation SAS AF= 0.00186 (9/4826). AF 95% confidence interval is 0.000972. There are 0 homozygotes in gnomad4. There are 8 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USH1G | NM_173477.5 | c.1152C>T | p.Asp384= | synonymous_variant | 2/3 | ENST00000614341.5 | |
USH1G | NM_001282489.3 | c.843C>T | p.Asp281= | synonymous_variant | 2/3 | ||
USH1G | XM_011524296.2 | c.843C>T | p.Asp281= | synonymous_variant | 2/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USH1G | ENST00000614341.5 | c.1152C>T | p.Asp384= | synonymous_variant | 2/3 | 1 | NM_173477.5 | P1 | |
USH1G | ENST00000579243.1 | c.*751C>T | 3_prime_UTR_variant, NMD_transcript_variant | 2/3 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000788 AC: 12AN: 152222Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000229 AC: 57AN: 248762Hom.: 0 AF XY: 0.000304 AC XY: 41AN XY: 135020
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GnomAD4 exome AF: 0.000123 AC: 179AN: 1460522Hom.: 0 Cov.: 41 AF XY: 0.000147 AC XY: 107AN XY: 726548
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GnomAD4 genome AF: 0.0000788 AC: 12AN: 152340Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8AN XY: 74488
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Usher syndrome type 1G Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 31, 2013 | Asp384Asp in exon 2 of USH1G: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue, is not located within the splice consensus sequence and has been reported as a "probably neutral" vari ant (Le Quesne Stabej 2012). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jul 17, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at