rs17000462

Positions:

• chrX-133652718-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004484.4(GPC3):​c.1413+9012T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0475 in 111,864 control chromosomes in the GnomAD database, including 321 homozygotes. There are 1,412 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.047 (321 hom., 1412 hem., cov: 23)
• Consequence: GPC3 NM_004484.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.301

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPC3	NM_004484.4	c.1413+9012T>C		intron_variant		ENST00000370818.8	NP_004475.1
GPC3	NM_001164617.2	c.1482+9012T>C		intron_variant			NP_001158089.1
GPC3	NM_001164618.2	c.1365+9012T>C		intron_variant			NP_001158090.1
GPC3	NM_001164619.2	c.1251+9012T>C		intron_variant			NP_001158091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPC3	ENST00000370818.8	c.1413+9012T>C		intron_variant		1	NM_004484.4	ENSP00000359854	P1

Frequencies

GnomAD3 genomes AF: 0.0473 AC: 5288 AN: 111810 Hom.: 318 Cov.: 23 AF XY: 0.0411 AC XY: 1397 AN XY: 33958

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0215

Gnomad ASJ AF: 0.00717

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000748

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00844

Gnomad NFE AF: 0.000807

Gnomad OTH AF: 0.0384

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0475 AC: 5313 AN: 111864 Hom.: 321 Cov.: 23 AF XY: 0.0415 AC XY: 1412 AN XY: 34022

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.0214

Gnomad4 ASJ AF: 0.00717

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000750

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000807

Gnomad4 OTH AF: 0.0379

Alfa AF: 0.0406 Hom.: 180

Bravo AF: 0.0539

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.54
DANN	Benign	0.78

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

Other links and lift over

dbSNP: rs17000462; hg19: chrX-132786746;