rs80060313

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS1

The NM_133261.3(GIPC3):c.132G>C(p.Ala44Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000312 in 1,531,040 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0017 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

GIPC3
NM_133261.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.645

Publications

0 publications found

Variant links:

Genes affected

GIPC3 (HGNC:18183): (GIPC PDZ domain containing family member 3) The protein encoded by this gene belongs to the GIPC family. Studies in mice suggest that this gene is required for postnatal maturation of the hair bundle and long-term survival of hair cells and spiral ganglion in the ear. Mutations in this gene are associated with autosomal recessive deafness. [provided by RefSeq, Dec 2011]

GIPC3 Gene-Disease associations (from GenCC):

nonsyndromic genetic hearing loss
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
autosomal recessive nonsyndromic hearing loss 15
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

GIPC3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 19-3585729-G-C is Benign according to our data. Variant chr19-3585729-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 227377.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.645 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0017 (258/152090) while in subpopulation AFR AF = 0.00602 (250/41536). AF 95% confidence interval is 0.00541. There are 1 homozygotes in GnomAd4. There are 112 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIPC3	NM_133261.3 link	c.132G>C	p.Ala44Ala	synonymous_variant	Exon 1 of 6	ENST00000644452.3	NP_573568.1	Q8TF64
GIPC3	NM_001411144.1 link	c.132G>C	p.Ala44Ala	synonymous_variant	Exon 1 of 6		NP_001398073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIPC3	ENST00000644452.3 link	c.132G>C	p.Ala44Ala	synonymous_variant	Exon 1 of 6		NM_133261.3	ENSP00000493901.2		Q8TF64
GIPC3	ENST00000644946.1 link	c.132G>C	p.Ala44Ala	synonymous_variant	Exon 1 of 6			ENSP00000495068.1		A0A2R8Y651

Frequencies

GnomAD3 genomes

AF:

0.00169

AC:

257

AN:

151980

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00601

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000959

GnomAD2 exomes

AF:

0.000210

AC:

AN:

128644

AF XY:

0.000170

show subpopulations

Gnomad AFR exome

AF:

0.00545

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000428

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000159

AC:

219

AN:

1378950

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

680308

show subpopulations

African (AFR)

AF:

0.00656

AC:

196

AN:

29878

American (AMR)

AF:

0.0000867

AC:

AN:

34600

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24662

East Asian (EAS)

AF:

0.00

AC:

AN:

33410

South Asian (SAS)

AF:

0.00

AC:

AN:

77594

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46218

Middle Eastern (MID)

AF:

0.000392

AC:

AN:

5108

European-Non Finnish (NFE)

AF:

0.00000187

AC:

AN:

1070396

Other (OTH)

AF:

0.000280

AC:

AN:

57084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.00170

AC:

258

AN:

152090

Hom.:

Cov.:

AF XY:

0.00151

AC XY:

112

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.00602

AC:

250

AN:

41536

American (AMR)

AF:

0.000392

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10532

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67954

Other (OTH)

AF:

0.000949

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

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:

0.000543

Hom.:

Bravo

AF:

0.00181

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 25, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 13, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Apr 03, 2018

Eurofins Ntd Llc (ga)

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 11, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Ala44Ala in Exon 01 of GIPC3: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and it is not located within the splice consensus sequence. This variant has been identified in 3/31 8 African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.bro adinstitute.org; dbSNP rs80060313). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

8.4

(source)

DANN

Benign

0.90

PhyloP100

-0.65

PromoterAI

0.037

Neutral

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over