11-17520892-T-C

Position:

chr11-17520892-T-C

Variant summary

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

The NM_153676.4(USH1C):c.1188A>G(p.Pro396Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 1,613,522 control chromosomes in the GnomAD database, including 270,528 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 21597 hom., cov: 32)

Exomes 𝑓: 0.58 ( 248931 hom. )

Consequence

USH1C
NM_153676.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -2.07

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:

USH1C (HGNC:):

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=-0.92).

BP6

Variant 11-17520892-T-C is Benign according to our data. Variant chr11-17520892-T-C is described in ClinVar as [Benign]. Clinvar id is 47976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-17520892-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.07 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USH1C	NM_153676.4 linkuse as main transcript	c.1188A>G	p.Pro396Pro	synonymous_variant	14/27	ENST00000005226.12	NP_710142.1	Q9Y6N9-5
USH1C	NM_005709.4 linkuse as main transcript	c.1188A>G	p.Pro396Pro	synonymous_variant	14/21	ENST00000318024.9	NP_005700.2	Q9Y6N9-1A0A0S2Z4U9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USH1C	ENST00000005226.12 linkuse as main transcript	c.1188A>G	p.Pro396Pro	synonymous_variant	14/27	5	NM_153676.4	ENSP00000005226.7		Q9Y6N9-5
USH1C	ENST00000318024.9 linkuse as main transcript	c.1188A>G	p.Pro396Pro	synonymous_variant	14/21	1	NM_005709.4	ENSP00000317018.4		Q9Y6N9-1

Frequencies

GnomAD3 genomes

AF:

0.521

AC:

79131

AN:

151920

Hom.:

21579

Cov.:

show subpopulations

Gnomad AFR

AF:

0.345

Gnomad AMI

AF:

0.646

Gnomad AMR

AF:

0.610

Gnomad ASJ

AF:

0.582

Gnomad EAS

AF:

0.660

Gnomad SAS

AF:

0.529

Gnomad FIN

AF:

0.557

Gnomad MID

AF:

0.503

Gnomad NFE

AF:

0.587

Gnomad OTH

AF:

0.519

GnomAD3 exomes

AF:

0.576

AC:

144888

AN:

251476

Hom.:

42720

AF XY:

0.573

AC XY:

77892

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.334

Gnomad AMR exome

AF:

0.670

Gnomad ASJ exome

AF:

0.586

Gnomad EAS exome

AF:

0.661

Gnomad SAS exome

AF:

0.525

Gnomad FIN exome

AF:

0.567

Gnomad NFE exome

AF:

0.583

Gnomad OTH exome

AF:

0.580

GnomAD4 exome

AF:

0.581

AC:

848790

AN:

1461484

Hom.:

248931

Cov.:

AF XY:

0.580

AC XY:

421370

AN XY:

727066

show subpopulations

Gnomad4 AFR exome

AF:

0.333

Gnomad4 AMR exome

AF:

0.664

Gnomad4 ASJ exome

AF:

0.577

Gnomad4 EAS exome

AF:

0.674

Gnomad4 SAS exome

AF:

0.523

Gnomad4 FIN exome

AF:

0.574

Gnomad4 NFE exome

AF:

0.588

Gnomad4 OTH exome

AF:

0.569

GnomAD4 genome

AF:

0.521

AC:

79190

AN:

152038

Hom.:

21597

Cov.:

AF XY:

0.523

AC XY:

38875

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.345

Gnomad4 AMR

AF:

0.610

Gnomad4 ASJ

AF:

0.582

Gnomad4 EAS

AF:

0.660

Gnomad4 SAS

AF:

0.529

Gnomad4 FIN

AF:

0.557

Gnomad4 NFE

AF:

0.587

Gnomad4 OTH

AF:

0.521

Alfa

AF:

0.565

Hom.:

31324

Bravo

AF:

0.516

Asia WGS

AF:

0.580

AC:

2015

AN:

3478

EpiCase

AF:

0.570

EpiControl

AF:

0.564

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jun 24, 2009	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Usher syndrome type 1C

Benign:3

Benign, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -

Autosomal recessive nonsyndromic hearing loss 18A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.98

DANN

Benign

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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