Variant X-133536266-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_004484.4(GPC3):c.1601A>G(p.Asp534Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000549 in 1,092,363 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 21)

Exomes 𝑓: 0.0000055 ( 0 hom. 2 hem. )

Consequence

GPC3
NM_004484.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.18

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13874897).

BP6

Variant X-133536266-T-C is Benign according to our data. Variant chrX-133536266-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 543095.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00000549 (6/1092363) while in subpopulation AMR AF= 0.00017 (6/35200). AF 95% confidence interval is 0.000074. There are 0 homozygotes in gnomad4_exome. There are 2 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Hemizygotes in GnomAdExome4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPC3	NM_004484.4 link	c.1601A>G	p.Asp534Gly	missense_variant	8/8	ENST00000370818.8	NP_004475.1	P51654-1Q53H15I6QTG3
GPC3	NM_001164617.2 link	c.1670A>G	p.Asp557Gly	missense_variant	9/9		NP_001158089.1	P51654-3Q53H15
GPC3	NM_001164618.2 link	c.1553A>G	p.Asp518Gly	missense_variant	8/8		NP_001158090.1	Q53H15B4DTD8
GPC3	NM_001164619.2 link	c.1439A>G	p.Asp480Gly	missense_variant	7/7		NP_001158091.1	P51654-2Q53H15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPC3	ENST00000370818.8 link	c.1601A>G	p.Asp534Gly	missense_variant	8/8	1	NM_004484.4	ENSP00000359854.3		P51654-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000383

AC:

AN:

182567

Hom.:

AF XY:

0.0000446

AC XY:

AN XY:

67337

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000255

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000549

AC:

AN:

1092363

Hom.:

Cov.:

AF XY:

0.00000559

AC XY:

AN XY:

357871

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000170

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

Cov.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Wilms tumor 1

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 03, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.50

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.36

T;.;.

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.83

T;T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

1.1

L;.;.

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.4

N;N;.

REVEL

Benign

0.12

Sift

Benign

0.053

T;D;.

Sift4G

Uncertain

0.027

D;D;D

Polyphen

0.92

P;.;.

Vest4

0.15

MutPred

0.55

Gain of catalytic residue at D534 (P = 0.1187);.;.;

MVP

0.50

MPC

0.35

ClinPred

0.19

GERP RS

4.8

Varity_R

0.28

gMVP

0.59

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