rs17776775

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_153676.4(USH1C):c.1770C>T(p.Ala590Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.055 in 1,600,338 control chromosomes in the GnomAD database, including 3,742 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.039 ( 212 hom., cov: 26)

Exomes 𝑓: 0.057 ( 3530 hom. )

Consequence

USH1C
NM_153676.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.752

Variant links:

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]

USH1C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 11-17509599-G-A is Benign according to our data. Variant chr11-17509599-G-A is described in ClinVar as [Benign]. Clinvar id is 47982.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-17509599-G-A is described in Lovd as [Benign]. Variant chr11-17509599-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.752 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USH1C	NM_153676.4 link	c.1770C>T	p.Ala590Ala	synonymous_variant	Exon 18 of 27	ENST00000005226.12	NP_710142.1	Q9Y6N9-5
USH1C	NM_005709.4 link	c.1285-7619C>T		intron_variant	Intron 15 of 20	ENST00000318024.9	NP_005700.2	Q9Y6N9-1A0A0S2Z4U9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USH1C	ENST00000005226.12 link	c.1770C>T	p.Ala590Ala	synonymous_variant	Exon 18 of 27	5	NM_153676.4	ENSP00000005226.7		Q9Y6N9-5
USH1C	ENST00000318024.9 link	c.1285-7619C>T		intron_variant	Intron 15 of 20	1	NM_005709.4	ENSP00000317018.4		Q9Y6N9-1

Frequencies

GnomAD3 genomes

AF:

0.0396

AC:

5954

AN:

150506

Hom.:

212

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0138

Gnomad AMI

AF:

0.0198

Gnomad AMR

AF:

0.0335

Gnomad ASJ

AF:

0.0341

Gnomad EAS

AF:

0.0347

Gnomad SAS

AF:

0.174

Gnomad FIN

AF:

0.0356

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0491

Gnomad OTH

AF:

0.0378

GnomAD3 exomes

AF:

0.0610

AC:

13848

AN:

227166

Hom.:

814

AF XY:

0.0687

AC XY:

8475

AN XY:

123390

show subpopulations

Gnomad AFR exome

AF:

0.0156

Gnomad AMR exome

AF:

0.0270

Gnomad ASJ exome

AF:

0.0363

Gnomad EAS exome

AF:

0.0268

Gnomad SAS exome

AF:

0.196

Gnomad FIN exome

AF:

0.0395

Gnomad NFE exome

AF:

0.0521

Gnomad OTH exome

AF:

0.0569

GnomAD4 exome

AF:

0.0566

AC:

82057

AN:

1449716

Hom.:

3530

Cov.:

AF XY:

0.0605

AC XY:

43540

AN XY:

719888

show subpopulations

Gnomad4 AFR exome

AF:

0.0132

Gnomad4 AMR exome

AF:

0.0278

Gnomad4 ASJ exome

AF:

0.0349

Gnomad4 EAS exome

AF:

0.0359

Gnomad4 SAS exome

AF:

0.195

Gnomad4 FIN exome

AF:

0.0344

Gnomad4 NFE exome

AF:

0.0505

Gnomad4 OTH exome

AF:

0.0583

GnomAD4 genome

AF:

0.0395

AC:

5948

AN:

150622

Hom.:

212

Cov.:

AF XY:

0.0406

AC XY:

2981

AN XY:

73470

show subpopulations

Gnomad4 AFR

AF:

0.0138

Gnomad4 AMR

AF:

0.0335

Gnomad4 ASJ

AF:

0.0341

Gnomad4 EAS

AF:

0.0347

Gnomad4 SAS

AF:

0.174

Gnomad4 FIN

AF:

0.0356

Gnomad4 NFE

AF:

0.0491

Gnomad4 OTH

AF:

0.0374

Alfa

AF:

0.0470

Hom.:

Bravo

AF:

0.0369

Asia WGS

AF:

0.0990

AC:

345

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Jun 24, 2009

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 05, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

May 25, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:3

Dec 13, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 09, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive nonsyndromic hearing loss 18A

Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Usher syndrome type 1C

Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

6.4

DANN

Benign

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over