rs187975106

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_001164375.3(C10orf105):c.*3111C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000697 in 1,608,272 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00058 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00071 ( 0 hom. )

Consequence

C10orf105
NM_001164375.3 3_prime_UTR

Scores

Splicing: ADA: 0.0002930

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:3

Conservation

PhyloP100: -1.16

Publications

0 publications found

Variant links:

Genes affected

C10orf105 (HGNC:20304): (chromosome 10 open reading frame 105) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

C10orf105 links:

CDH23 (HGNC:13733): (cadherin related 23) This gene is a member of the cadherin superfamily, whose genes encode calcium dependent cell-cell adhesion glycoproteins. The encoded protein is thought to be involved in stereocilia organization and hair bundle formation. The gene is located in a region containing the human deafness loci DFNB12 and USH1D. Usher syndrome 1D and nonsyndromic autosomal recessive deafness DFNB12 are caused by allelic mutations of this cadherin-like gene. Upregulation of this gene may also be associated with breast cancer. Alternative splice variants encoding different isoforms have been described. [provided by RefSeq, May 2013]

CDH23 Gene-Disease associations (from GenCC):

autosomal recessive nonsyndromic hearing loss 12
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
nonsyndromic genetic hearing loss
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Usher syndrome type 1
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
Usher syndrome type 1D
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CDH23 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 10-71712825-G-A is Benign according to our data. Variant chr10-71712825-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 300424.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
C10orf105	NM_001164375.3 link	c.*3111C>T	3_prime_UTR_variant	Exon 2 of 2	ENST00000441508.4	NP_001157847.1
CDH23	NM_022124.6 link	c.3369+12G>A	intron_variant	Intron 28 of 69	ENST00000224721.12	NP_071407.4
C10orf105	NM_001168390.2 link	c.*3111C>T	3_prime_UTR_variant	Exon 2 of 2		NP_001161862.1
CDH23	NM_001171930.2 link	c.3369+12G>A	intron_variant	Intron 28 of 31		NP_001165401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C10orf105	ENST00000441508.4 link	c.*3111C>T		3_prime_UTR_variant	Exon 2 of 2	1	NM_001164375.3	ENSP00000403151.2
CDH23	ENST00000224721.12 link	c.3369+12G>A		intron_variant	Intron 28 of 69	5	NM_022124.6	ENSP00000224721.9

Frequencies

GnomAD3 genomes

AF:

0.000584

AC:

AN:

152268

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000530

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000911

Gnomad OTH

AF:

0.000957

GnomAD2 exomes

AF:

0.000392

AC:

AN:

234600

AF XY:

0.000399

show subpopulations

Gnomad AFR exome

AF:

0.000498

Gnomad AMR exome

AF:

0.000422

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000620

Gnomad OTH exome

AF:

0.000347

GnomAD4 exome

AF:

0.000709

AC:

1032

AN:

1455886

Hom.:

Cov.:

AF XY:

0.000672

AC XY:

486

AN XY:

723650

show subpopulations

African (AFR)

AF:

0.000539

AC:

AN:

33402

American (AMR)

AF:

0.000411

AC:

AN:

43848

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25994

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39516

South Asian (SAS)

AF:

0.000117

AC:

AN:

85162

European-Finnish (FIN)

AF:

0.0000191

AC:

AN:

52330

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.000846

AC:

939

AN:

1109732

Other (OTH)

AF:

0.000748

AC:

AN:

60144

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

108

162

216

270

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

114

152

190

<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:

0.000584

AC:

AN:

152386

Hom.:

Cov.:

AF XY:

0.000537

AC XY:

AN XY:

74518

show subpopulations

African (AFR)

AF:

0.000529

AC:

AN:

41600

American (AMR)

AF:

0.000131

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000911

AC:

AN:

68042

Other (OTH)

AF:

0.000947

AC:

AN:

2112

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

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:

0.000385

Hom.:

Bravo

AF:

0.000491

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Usher syndrome type 1D

Uncertain:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

Autosomal recessive nonsyndromic hearing loss 12

Uncertain:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:1

Apr 03, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

c.3369+12G>A in intron 28 of CDH23: This variant is not expected to have clinica l significance because it is not located within the splice consensus sequence an d has been identified in 17/49721 European American chromosomes by the Exome Agg regation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs187975106).

CDH23-related disorder

Benign:1

Aug 30, 2024

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

not provided

Benign:1

Jan 11, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely 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

-0.86

CADD

Benign

0.0060

(source)

DANN

Benign

0.73

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00029

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over