Variant 19-14479468-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005716.4(GIPC1):c.712A>C(p.Thr238Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000891 in 1,436,948 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000081 ( 0 hom. )

Consequence

GIPC1
NM_005716.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.37

Variant links:

Genes affected

GIPC1 (HGNC:1226): (GIPC PDZ domain containing family member 1) GIPC1 is a scaffolding protein that regulates cell surface receptor expression and trafficking (Lee et al., 2008 [PubMed 18775991]).[supplied by OMIM, Apr 2009]

GIPC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.049288213).

BS2

High AC in GnomAd4 at 24 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GIPC1	NM_005716.4 linkuse as main transcript	c.712A>C	p.Thr238Pro	missense_variant	7/9	ENST00000393033.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GIPC1	ENST00000393033.9 linkuse as main transcript	c.712A>C	p.Thr238Pro	missense_variant	7/9	1	NM_005716.4	P1	O14908-1

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.000754

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000277

AC:

AN:

75874

Hom.:

AF XY:

0.000288

AC XY:

AN XY:

41708

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000570

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000778

Gnomad FIN exome

AF:

0.000370

Gnomad NFE exome

AF:

0.000113

Gnomad OTH exome

AF:

0.00132

GnomAD4 exome

AF:

0.0000810

AC:

104

AN:

1284642

Hom.:

Cov.:

AF XY:

0.0000987

AC XY:

AN XY:

628208

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000391

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000545

Gnomad4 FIN exome

AF:

0.000317

Gnomad4 NFE exome

AF:

0.0000301

Gnomad4 OTH exome

AF:

0.000210

GnomAD4 genome

AF:

0.000158

AC:

AN:

152306

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.000754

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.0000839

Hom.:

Bravo

AF:

0.000151

ExAC

AF:

0.000186

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 27, 2022

The c.712A>C (p.T238P) alteration is located in exon 7 (coding exon 4) of the GIPC1 gene. This alteration results from a A to C substitution at nucleotide position 712, causing the threonine (T) at amino acid position 238 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Uncertain

-0.010

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.032

Eigen_PC

Benign

0.062

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.56

T;.;.;T;T;.;T

MetaRNN

Benign

0.049

T;T;T;T;T;T;T

MetaSVM

Uncertain

0.023

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-2.4

N;D;D;.;.;.;.

REVEL

Uncertain

0.49

Sift

Benign

0.055

T;D;D;.;.;.;.

Sift4G

Benign

0.089

T;T;T;D;T;T;T

Polyphen

0.0050

.;B;B;.;B;.;.

Vest4

0.14

MutPred

0.19

.;Loss of phosphorylation at T238 (P = 0.0171);Loss of phosphorylation at T238 (P = 0.0171);.;Loss of phosphorylation at T238 (P = 0.0171);.;.;

MVP

0.94

MPC

0.24

ClinPred

0.046

GERP RS

4.3

Varity_R

0.67

gMVP

0.77

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