rs142545736
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1
The NM_153676.4(USH1C):c.1632C>T(p.Asp544Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00021 in 1,601,922 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.0010 ( 0 hom., cov: 29)
Exomes 𝑓: 0.00012 ( 0 hom. )
Consequence
USH1C
NM_153676.4 synonymous
NM_153676.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.194
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 Benign. Variant got -15 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
Variant 11-17509737-G-A is Benign according to our data. Variant chr11-17509737-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 166380.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.194 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00103 (157/151714) while in subpopulation AFR AF= 0.00351 (145/41336). AF 95% confidence interval is 0.00304. There are 0 homozygotes in gnomad4. There are 74 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| USH1C | NM_153676.4 | c.1632C>T | p.Asp544Asp | synonymous_variant | Exon 18 of 27 | ENST00000005226.12 | NP_710142.1 | |
| USH1C | NM_005709.4 | c.1284+7664C>T | intron_variant | Intron 15 of 20 | ENST00000318024.9 | NP_005700.2 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| USH1C | ENST00000005226.12 | c.1632C>T | p.Asp544Asp | synonymous_variant | Exon 18 of 27 | 5 | NM_153676.4 | ENSP00000005226.7 | ||
| USH1C | ENST00000318024.9 | c.1284+7664C>T | intron_variant | Intron 15 of 20 | 1 | NM_005709.4 | ENSP00000317018.4 |
Frequencies
GnomAD3 genomes 0.00104 AC: 157AN: 151596Hom.: 0 Cov.: 29
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GnomAD3 exomes AF: 0.000191 AC: 46AN: 240246Hom.: 0 AF XY: 0.000161 AC XY: 21AN XY: 130734
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GnomAD4 exome AF: 0.000124 AC: 180AN: 1450208Hom.: 0 Cov.: 40 AF XY: 0.000103 AC XY: 74AN XY: 721674
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GnomAD4 genome 0.00103 AC: 157AN: 151714Hom.: 0 Cov.: 29 AF XY: 0.000998 AC XY: 74AN XY: 74126
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Mar 29, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
May 06, 2021
GeneDx
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
not specified Benign:1
May 07, 2012
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
Asp544Asp in Exon 18 of USH1C: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 0.3% (13/3738) of Af rican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs142545736). -
Computational scores
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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