rs397517876
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_153676.4(USH1C):c.2418C>T(p.Asn806=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,614,054 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 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000096 ( 0 hom. )
Consequence
USH1C
NM_153676.4 synonymous
NM_153676.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.262
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 -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
?
Variant 11-17498234-G-A is Benign according to our data. Variant chr11-17498234-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 48001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.262 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USH1C | NM_153676.4 | c.2418C>T | p.Asn806= | synonymous_variant | 24/27 | ENST00000005226.12 | |
USH1C | NM_005709.4 | c.1518C>T | p.Asn506= | synonymous_variant | 19/21 | ENST00000318024.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USH1C | ENST00000005226.12 | c.2418C>T | p.Asn806= | synonymous_variant | 24/27 | 5 | NM_153676.4 | ||
USH1C | ENST00000318024.9 | c.1518C>T | p.Asn506= | synonymous_variant | 19/21 | 1 | NM_005709.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152174Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251474Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135904
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GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461880Hom.: 0 Cov.: 35 AF XY: 0.0000110 AC XY: 8AN XY: 727240
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152174Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74334
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 22, 2013 | Asn806Asn in exon 24 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. - |
Usher syndrome type 1C;C1865870:Autosomal recessive nonsyndromic hearing loss 18A Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Counsyl | Jun 26, 2017 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2023 | - - |
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