Variant chr19-3585647-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_133261.3(GIPC3):c.50C>T(p.Ala17Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000166 in 1,206,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 9.5e-7 ( 0 hom. )

Consequence

GIPC3
NM_133261.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.109

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12055811).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GIPC3	NM_133261.3 linkuse as main transcript	c.50C>T	p.Ala17Val	missense_variant	1/6	ENST00000644452.3	NP_573568.1
GIPC3	NM_001411144.1 linkuse as main transcript	c.50C>T	p.Ala17Val	missense_variant	1/6		NP_001398073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GIPC3	ENST00000644452.3 linkuse as main transcript	c.50C>T	p.Ala17Val	missense_variant	1/6		NM_133261.3	ENSP00000493901	P1
GIPC3	ENST00000644946.1 linkuse as main transcript	c.50C>T	p.Ala17Val	missense_variant	1/6			ENSP00000495068

Frequencies

GnomAD3 genomes

AF:

0.00000662

AC:

AN:

150984

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

9.47e-7

AC:

AN:

1055670

Hom.:

Cov.:

AF XY:

0.00000199

AC XY:

AN XY:

503490

show subpopulations

Gnomad4 AFR exome

AF:

0.0000470

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000662

AC:

AN:

150984

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73696

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

T;T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.42

.;T;T

M_CAP

Pathogenic

0.30

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.0

N;N;.

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.2

N;.;.

REVEL

Benign

0.18

Sift

Benign

0.23

T;.;.

Sift4G

Benign

0.29

T;.;.

Polyphen

0.0040

B;B;.

Vest4

0.040

MutPred

0.12

Loss of glycosylation at P15 (P = 0.1627);Loss of glycosylation at P15 (P = 0.1627);Loss of glycosylation at P15 (P = 0.1627);

MVP

0.63

MPC

0.098

ClinPred

0.13

GERP RS

2.5

Varity_R

0.050

gMVP

0.29

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over