rs8113232

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_133261.3(GIPC3):c.276G>A(p.Leu92Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,613,494 control chromosomes in the GnomAD database, including 23,097 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 6459 hom., cov: 31)

Exomes 𝑓: 0.13 ( 16638 hom. )

Consequence

GIPC3
NM_133261.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.913

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 19-3586545-G-A is Benign according to our data. Variant chr19-3586545-G-A is described in ClinVar as [Benign]. Clinvar id is 46571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.913 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIPC3	NM_133261.3 link	c.276G>A	p.Leu92Leu	synonymous_variant	Exon 2 of 6	ENST00000644452.3	NP_573568.1	Q8TF64
GIPC3	NM_001411144.1 link	c.276G>A	p.Leu92Leu	synonymous_variant	Exon 2 of 6		NP_001398073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIPC3	ENST00000644452.3 link	c.276G>A	p.Leu92Leu	synonymous_variant	Exon 2 of 6		NM_133261.3	ENSP00000493901.2		Q8TF64
GIPC3	ENST00000644946.1 link	c.276G>A	p.Leu92Leu	synonymous_variant	Exon 2 of 6			ENSP00000495068.1		A0A2R8Y651

Frequencies

GnomAD3 genomes

AF:

0.229

AC:

34745

AN:

151990

Hom.:

6432

Cov.:

show subpopulations

Gnomad AFR

AF:

0.517

Gnomad AMI

AF:

0.0800

Gnomad AMR

AF:

0.132

Gnomad ASJ

AF:

0.122

Gnomad EAS

AF:

0.0512

Gnomad SAS

AF:

0.121

Gnomad FIN

AF:

0.0837

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.128

Gnomad OTH

AF:

0.187

GnomAD3 exomes

AF:

0.137

AC:

34256

AN:

250884

Hom.:

3916

AF XY:

0.130

AC XY:

17681

AN XY:

135786

show subpopulations

Gnomad AFR exome

AF:

0.532

Gnomad AMR exome

AF:

0.0816

Gnomad ASJ exome

AF:

0.114

Gnomad EAS exome

AF:

0.0486

Gnomad SAS exome

AF:

0.126

Gnomad FIN exome

AF:

0.0874

Gnomad NFE exome

AF:

0.126

Gnomad OTH exome

AF:

0.123

GnomAD4 exome

AF:

0.133

AC:

194965

AN:

1461386

Hom.:

16638

Cov.:

AF XY:

0.132

AC XY:

95623

AN XY:

727008

show subpopulations

Gnomad4 AFR exome

AF:

0.541

Gnomad4 AMR exome

AF:

0.0878

Gnomad4 ASJ exome

AF:

0.113

Gnomad4 EAS exome

AF:

0.0495

Gnomad4 SAS exome

AF:

0.125

Gnomad4 FIN exome

AF:

0.0897

Gnomad4 NFE exome

AF:

0.128

Gnomad4 OTH exome

AF:

0.152

GnomAD4 genome

AF:

0.229

AC:

34820

AN:

152108

Hom.:

6459

Cov.:

AF XY:

0.222

AC XY:

16520

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.517

Gnomad4 AMR

AF:

0.132

Gnomad4 ASJ

AF:

0.122

Gnomad4 EAS

AF:

0.0511

Gnomad4 SAS

AF:

0.121

Gnomad4 FIN

AF:

0.0837

Gnomad4 NFE

AF:

0.128

Gnomad4 OTH

AF:

0.185

Alfa

AF:

0.143

Hom.:

3723

Bravo

AF:

0.244

Asia WGS

AF:

0.126

AC:

439

AN:

3478

EpiCase

AF:

0.128

EpiControl

AF:

0.126

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Leu92Leu in Exon 02 of GIPC3: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 48.7% (1820/3738) of African American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs8113232). -

Feb 26, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 09, 2017

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. -

not provided

Benign:2

Feb 03, 2025

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

2.0

DANN

Benign

0.66

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