Variant chr19-14479437-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_005716.4(GIPC1):c.743G>A(p.Arg248Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000704 in 1,421,344 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R248W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000071 ( 0 hom. )

Consequence

GIPC1
NM_005716.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.20

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.23293963).

BS2

High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GIPC1	NM_005716.4 linkuse as main transcript	c.743G>A	p.Arg248Gln	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.743G>A	p.Arg248Gln	missense_variant	7/9	1	NM_005716.4	P1	O14908-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000137

AC:

AN:

72920

Hom.:

AF XY:

0.00

AC XY:

AN XY:

40148

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000283

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000709

AC:

AN:

1269146

Hom.:

Cov.:

AF XY:

0.00000647

AC XY:

AN XY:

618314

show subpopulations

Gnomad4 AFR exome

AF:

0.0000402

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:

0.00000688

Gnomad4 OTH exome

AF:

0.0000193

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000420

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000169

AC:

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

May 30, 2023

The c.743G>A (p.R248Q) alteration is located in exon 7 (coding exon 4) of the GIPC1 gene. This alteration results from a G to A substitution at nucleotide position 743, causing the arginine (R) at amino acid position 248 to be replaced by a glutamine (Q). 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

0.099

BayesDel_addAF

Benign

-0.021

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.70

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

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.23

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

MetaSVM

Benign

-0.59

MutationTaster

Benign

0.90

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

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.88

N;N;N;.;.;.;.

REVEL

Benign

0.23

Sift

Benign

0.17

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

Sift4G

Benign

0.24

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

Polyphen

0.011

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

Vest4

0.17

MVP

0.93

MPC

0.22

ClinPred

0.40

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.075

gMVP

0.36

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