Variant rs143968967 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_133261.3(GIPC3):c.226-7C>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000554 in 1,612,884 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00093 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00051 ( 4 hom. )

Consequence

GIPC3
NM_133261.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.001416

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.20

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 19-3586488-C-G is Benign according to our data. Variant chr19-3586488-C-G is described in ClinVar as [Benign]. Clinvar id is 504572.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GIPC3	NM_133261.3 linkuse as main transcript	c.226-7C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000644452.3	NP_573568.1
GIPC3	NM_001411144.1 linkuse as main transcript	c.226-7C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_001398073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GIPC3	ENST00000644452.3 linkuse as main transcript	c.226-7C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NM_133261.3	ENSP00000493901	P1
GIPC3	ENST00000644946.1 linkuse as main transcript	c.226-7C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant				ENSP00000495068

Frequencies

GnomAD3 genomes

AF:

0.000934

AC:

142

AN:

152050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0103

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00108

AC:

269

AN:

249330

Hom.:

AF XY:

0.000946

AC XY:

128

AN XY:

135318

show subpopulations

Gnomad AFR exome

AF:

0.000250

Gnomad AMR exome

AF:

0.0000869

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00949

Gnomad NFE exome

AF:

0.000507

Gnomad OTH exome

AF:

0.000493

GnomAD4 exome

AF:

0.000514

AC:

751

AN:

1460716

Hom.:

Cov.:

AF XY:

0.000480

AC XY:

349

AN XY:

726664

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00761

Gnomad4 NFE exome

AF:

0.000291

Gnomad4 OTH exome

AF:

0.000331

GnomAD4 genome

AF:

0.000933

AC:

142

AN:

152168

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

105

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0000723

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0103

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000274

Hom.:

Bravo

AF:

0.000272

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Oct 06, 2016

c.226-7C>G in intron 1 of GIPC3: This variant is not expected to have clinical s ignificance because it has been identified in 0.9% (57/6494) of Finnish chromoso mes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; d bSNP rs143968967). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.78

DANN

Benign

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0014

dbscSNV1_RF

Benign

0.18

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