rs111033520

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_153676.4(USH1C):c.1792C>T(p.Arg598Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000556 in 1,600,762 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R598H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 26)

Exomes 𝑓: 0.000056 ( 1 hom. )

Consequence

USH1C
NM_153676.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.582

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

Usher syndrome type 1
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
Usher syndrome type 1C
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, PanelApp Australia
autosomal recessive nonsyndromic hearing loss 18A
Inheritance: AR, Unknown Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
nonsyndromic genetic hearing loss
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

USH1C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.042703062).

BP6

Variant 11-17509577-G-A is Benign according to our data. Variant chr11-17509577-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 47983.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153676.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
USH1C	NM_153676.4	MANE Select	c.1792C>T	p.Arg598Cys	missense	Exon 18 of 27	NP_710142.1
USH1C	NM_005709.4	MANE Plus Clinical	c.1285-7597C>T		intron	N/A	NP_005700.2
USH1C	NM_001440679.1		c.1470+2325C>T		intron	N/A	NP_001427608.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
USH1C	ENST00000005226.12	TSL:5 MANE Select	c.1792C>T	p.Arg598Cys	missense	Exon 18 of 27	ENSP00000005226.7
USH1C	ENST00000318024.9	TSL:1 MANE Plus Clinical	c.1285-7597C>T		intron	N/A	ENSP00000317018.4
USH1C	ENST00000527020.5	TSL:1	c.1228-7597C>T		intron	N/A	ENSP00000436934.1

Frequencies

GnomAD3 genomes

AF:

0.0000529

AC:

AN:

151118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000590

Gnomad SAS

AF:

0.00107

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000955

AC:

AN:

230416

AF XY:

0.000144

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000114

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000290

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000559

AC:

AN:

1449532

Hom.:

Cov.:

AF XY:

0.0000876

AC XY:

AN XY:

719422

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33398

American (AMR)

AF:

0.00

AC:

AN:

44036

Ashkenazi Jewish (ASJ)

AF:

0.0000388

AC:

AN:

25766

East Asian (EAS)

AF:

0.0000762

AC:

AN:

39392

South Asian (SAS)

AF:

0.000709

AC:

AN:

84616

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50180

Middle Eastern (MID)

AF:

0.000180

AC:

AN:

5548

European-Non Finnish (NFE)

AF:

0.0000127

AC:

AN:

1106582

Other (OTH)

AF:

0.0000333

AC:

AN:

60014

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000529

AC:

AN:

151230

Hom.:

Cov.:

AF XY:

0.0000677

AC XY:

AN XY:

73830

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41188

American (AMR)

AF:

0.00

AC:

AN:

15158

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.000591

AC:

AN:

5072

South Asian (SAS)

AF:

0.00107

AC:

AN:

4684

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10522

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67834

Other (OTH)

AF:

0.00

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.000115

AC:

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.52

CADD

Uncertain

(source)

DANN

Uncertain

1.0

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.66

M_CAP

Benign

0.066

MetaRNN

Benign

0.043

MetaSVM

Benign

-1.1

PhyloP100

0.58

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.9

REVEL

Benign

0.072

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.053

Vest4

0.27

MutPred

0.20

Loss of solvent accessibility (P = 0.0352)

MVP

0.39

MPC

0.082

ClinPred

0.061

GERP RS

4.6

gMVP

0.30

Mutation Taster

=89/11

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over