Variant rs143561452 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The ENST00000370818.8(GPC3):c.394A>G(p.Asn132Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000584 in 1,096,547 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 24 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N132K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.000058 ( 0 hom. 24 hem. )

Consequence

GPC3
ENST00000370818.8 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.05

Variant links:

Genes affected

GPC3 (HGNC:4451): (glypican 3) Cell surface heparan sulfate proteoglycans are composed of a membrane-associated protein core substituted with a variable number of heparan sulfate chains. Members of the glypican-related integral membrane proteoglycan family (GRIPS) contain a core protein anchored to the cytoplasmic membrane via a glycosyl phosphatidylinositol linkage. These proteins may play a role in the control of cell division and growth regulation. The protein encoded by this gene can bind to and inhibit the dipeptidyl peptidase activity of CD26, and it can induce apoptosis in certain cell types. Deletion mutations in this gene are associated with Simpson-Golabi-Behmel syndrome, also known as Simpson dysmorphia syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

GPC3 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=0.24746102).

BP6

Variant X-133754120-T-C is Benign according to our data. Variant chrX-133754120-T-C is described in ClinVar as [Benign]. Clinvar id is 579381.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 24 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPC3	NM_004484.4 linkuse as main transcript	c.394A>G	p.Asn132Asp	missense_variant	3/8	ENST00000370818.8	NP_004475.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPC3	ENST00000370818.8 linkuse as main transcript	c.394A>G	p.Asn132Asp	missense_variant	3/8	1	NM_004484.4	ENSP00000359854	P1	P51654-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000440

AC:

AN:

181997

Hom.:

AF XY:

0.0000747

AC XY:

AN XY:

66975

show subpopulations

Gnomad AFR exome

AF:

0.000152

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:

0.0000743

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000584

AC:

AN:

1096547

Hom.:

Cov.:

AF XY:

0.0000663

AC XY:

AN XY:

361943

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

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:

0.0000737

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Wilms tumor 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 14, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.44

T;.;.

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.82

T;T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.25

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.2

L;L;.

MutationTaster

Benign

0.99

N;N;N

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-2.7

D;D;.

REVEL

Benign

0.15

Sift

Benign

0.070

T;T;.

Sift4G

Uncertain

0.047

D;D;T

Polyphen

0.24

B;.;.

Vest4

0.35

MVP

0.68

MPC

0.23

ClinPred

0.078

GERP RS

5.3

Varity_R

0.47

gMVP

0.43

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