rs142801489
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_153676.4(USH1C):c.2487C>T(p.Gly829Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00013 in 1,613,768 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 0.00031 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
USH1C
NM_153676.4 synonymous
NM_153676.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0430
Genes affected
USH1C (HGNC:12597): (USH1 protein network component harmonin) This gene encodes a scaffold protein that functions in the assembly of Usher protein complexes. The protein contains PDZ domains, a coiled-coil region with a bipartite nuclear localization signal and a PEST degradation sequence. Defects in this gene are the cause of Usher syndrome type 1C and non-syndromic sensorineural deafness autosomal recessive type 18. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP7
Synonymous conserved (PhyloP=0.043 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
USH1C | NM_153676.4 | c.2487C>T | p.Gly829Gly | synonymous_variant | 24/27 | ENST00000005226.12 | NP_710142.1 | |
USH1C | NM_005709.4 | c.1587C>T | p.Gly529Gly | synonymous_variant | 19/21 | ENST00000318024.9 | NP_005700.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
USH1C | ENST00000005226.12 | c.2487C>T | p.Gly829Gly | synonymous_variant | 24/27 | 5 | NM_153676.4 | ENSP00000005226.7 | ||
USH1C | ENST00000318024.9 | c.1587C>T | p.Gly529Gly | synonymous_variant | 19/21 | 1 | NM_005709.4 | ENSP00000317018.4 |
Frequencies
GnomAD3 genomes AF: 0.000289 AC: 44AN: 152174Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000155 AC: 39AN: 251284Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135800
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GnomAD4 exome AF: 0.000112 AC: 163AN: 1461476Hom.: 0 Cov.: 30 AF XY: 0.0000949 AC XY: 69AN XY: 727082
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GnomAD4 genome AF: 0.000309 AC: 47AN: 152292Hom.: 0 Cov.: 33 AF XY: 0.000349 AC XY: 26AN XY: 74466
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 30, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 13, 2020 | See Variant Classification Assertion Criteria. - |
Usher syndrome type 1C;C1865870:Autosomal recessive nonsyndromic hearing loss 18A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Mar 07, 2018 | - - |
Usher syndrome type 1C Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at