rs200239508
Positions:
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_153676.4(USH1C):āc.186T>Cā(p.Ile62=) variant causes a synonymous change. The variant allele was found at a frequency of 0.000162 in 1,613,964 control chromosomes in the GnomAD database, including 1 homozygotes. 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: š 0.00018 ( 0 hom., cov: 33)
Exomes š: 0.00016 ( 1 hom. )
Consequence
USH1C
NM_153676.4 synonymous
NM_153676.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.61
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]
Genome browser will be placed here
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=-0.51).
BP6
?
Variant 11-17531461-A-G is Benign according to our data. Variant chr11-17531461-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 166394.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1, Benign=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USH1C | NM_153676.4 | c.186T>C | p.Ile62= | synonymous_variant | 3/27 | ENST00000005226.12 | |
USH1C | NM_005709.4 | c.186T>C | p.Ile62= | synonymous_variant | 3/21 | ENST00000318024.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USH1C | ENST00000005226.12 | c.186T>C | p.Ile62= | synonymous_variant | 3/27 | 5 | NM_153676.4 | ||
USH1C | ENST00000318024.9 | c.186T>C | p.Ile62= | synonymous_variant | 3/21 | 1 | NM_005709.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000177 AC: 27AN: 152158Hom.: 0 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
27
AN:
152158
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000271 AC: 68AN: 251340Hom.: 0 AF XY: 0.000258 AC XY: 35AN XY: 135864
GnomAD3 exomes
AF:
AC:
68
AN:
251340
Hom.:
AF XY:
AC XY:
35
AN XY:
135864
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000160 AC: 234AN: 1461806Hom.: 1 Cov.: 32 AF XY: 0.000175 AC XY: 127AN XY: 727196
GnomAD4 exome
AF:
AC:
234
AN:
1461806
Hom.:
Cov.:
32
AF XY:
AC XY:
127
AN XY:
727196
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000177 AC: 27AN: 152158Hom.: 0 Cov.: 33 AF XY: 0.000215 AC XY: 16AN XY: 74326
GnomAD4 genome
?
AF:
AC:
27
AN:
152158
Hom.:
Cov.:
33
AF XY:
AC XY:
16
AN XY:
74326
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 19, 2021 | - - |
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. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 30, 2016 | p.Ile62Ile in Exon 3 of USH1C: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 24/66358 of Europea n chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstit ute.org; dbSNP rs200239508). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at