Variant X-133754180-TAAAA-TAAAAA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The ENST00000370818.8(GPC3):c.338-5_338-4insT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 23 hom., 186 hem., cov: 19)

Exomes 𝑓: 0.076 ( 1 hom. 18 hem. )

Consequence

GPC3
ENST00000370818.8 splice_region, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.883

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 -16 ACMG points.

BP6

Variant X-133754180-T-TA is Benign according to our data. Variant chrX-133754180-T-TA is described in ClinVar as [Likely_benign]. Clinvar id is 695314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPC3	NM_004484.4 linkuse as main transcript	c.338-5_338-4insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		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.338-5_338-4insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_004484.4	ENSP00000359854	P1	P51654-1

Frequencies

GnomAD3 genomes

AF:

0.0171

AC:

1308

AN:

76415

Hom.:

Cov.:

AF XY:

0.0104

AC XY:

186

AN XY:

17811

show subpopulations

Gnomad AFR

AF:

0.0463

Gnomad AMI

AF:

0.00866

Gnomad AMR

AF:

0.00497

Gnomad ASJ

AF:

0.00257

Gnomad EAS

AF:

0.00345

Gnomad SAS

AF:

0.00177

Gnomad FIN

AF:

0.0110

Gnomad MID

AF:

0.00704

Gnomad NFE

AF:

0.00667

Gnomad OTH

AF:

0.0121

GnomAD4 exome

AF:

0.0761

AC:

59912

AN:

787248

Hom.:

Cov.:

AF XY:

0.0000922

AC XY:

AN XY:

195282

show subpopulations

Gnomad4 AFR exome

AF:

0.0929

Gnomad4 AMR exome

AF:

0.0381

Gnomad4 ASJ exome

AF:

0.0668

Gnomad4 EAS exome

AF:

0.0562

Gnomad4 SAS exome

AF:

0.0514

Gnomad4 FIN exome

AF:

0.0524

Gnomad4 NFE exome

AF:

0.0813

Gnomad4 OTH exome

AF:

0.0724

GnomAD4 genome

AF:

0.0171

AC:

1305

AN:

76406

Hom.:

Cov.:

AF XY:

0.0104

AC XY:

186

AN XY:

17820

show subpopulations

Gnomad4 AFR

AF:

0.0461

Gnomad4 AMR

AF:

0.00497

Gnomad4 ASJ

AF:

0.00257

Gnomad4 EAS

AF:

0.00308

Gnomad4 SAS

AF:

0.00179

Gnomad4 FIN

AF:

0.0110

Gnomad4 NFE

AF:

0.00668

Gnomad4 OTH

AF:

0.0130

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -

Hereditary cancer-predisposing syndrome

Benign:1

Benign, criteria provided, single submitter

curation

Sema4, Sema4

Feb 24, 2020

- -

Wilms tumor 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Simpson-Golabi-Behmel syndrome type 1;CN033288:Wilms tumor 1

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Jan 06, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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