Variant chrX-133535890-TTTTC-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_004484.4(GPC3):c.*230_*233del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0208 in 382,694 control chromosomes in the GnomAD database, including 565 homozygotes. There are 1,899 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.052 ( 413 hom., 1341 hem., cov: 20)

Exomes 𝑓: 0.0082 ( 152 hom. 558 hem. )

Consequence

GPC3
NM_004484.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.15

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 -10 ACMG points.

BP6

Variant X-133535890-TTTTC-T is Benign according to our data. Variant chrX-133535890-TTTTC-T is described in ClinVar as [Benign]. Clinvar id is 1246217.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
GPC3	NM_004484.4 linkuse as main transcript	c.230_233del	3_prime_UTR_variant	8/8	ENST00000370818.8
GPC3	NM_001164617.2 linkuse as main transcript	c.230_233del	3_prime_UTR_variant	9/9
GPC3	NM_001164618.2 linkuse as main transcript	c.230_233del	3_prime_UTR_variant	8/8
GPC3	NM_001164619.2 linkuse as main transcript	c.230_233del	3_prime_UTR_variant	7/7

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPC3	ENST00000370818.8 linkuse as main transcript	c.230_233del	3_prime_UTR_variant	8/8	1	NM_004484.4	P1	P51654-1
GPC3	ENST00000394299.7 linkuse as main transcript	c.230_233del	3_prime_UTR_variant	9/9	1			P51654-3
GPC3	ENST00000669691.1 linkuse as main transcript	n.1039_1042del	non_coding_transcript_exon_variant	6/6

Frequencies

GnomAD3 genomes

AF:

0.0520

AC:

5712

AN:

109894

Hom.:

411

Cov.:

AF XY:

0.0413

AC XY:

1331

AN XY:

32200

show subpopulations

Gnomad AFR

AF:

0.180

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0198

Gnomad ASJ

AF:

0.00723

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000784

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00844

Gnomad NFE

AF:

0.000587

Gnomad OTH

AF:

0.0425

GnomAD4 exome

AF:

0.00821

AC:

2240

AN:

272757

Hom.:

152

AF XY:

0.00687

AC XY:

558

AN XY:

81189

show subpopulations

Gnomad4 AFR exome

AF:

0.189

Gnomad4 AMR exome

AF:

0.0127

Gnomad4 ASJ exome

AF:

0.00599

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000265

Gnomad4 FIN exome

AF:

0.0000517

Gnomad4 NFE exome

AF:

0.000355

Gnomad4 OTH exome

AF:

0.0166

GnomAD4 genome

AF:

0.0521

AC:

5726

AN:

109937

Hom.:

413

Cov.:

AF XY:

0.0416

AC XY:

1341

AN XY:

32253

show subpopulations

Gnomad4 AFR

AF:

0.180

Gnomad4 AMR

AF:

0.0198

Gnomad4 ASJ

AF:

0.00723

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000787

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000587

Gnomad4 OTH

AF:

0.0419

Alfa

AF:

0.0411

Hom.:

139

Bravo

AF:

0.0612

Asia WGS

AF:

0.0120

AC:

AN:

2518

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 03, 2018

- -

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