rs1264379

chrX-133931739-A-GchrX-133931739-A-T

Variant summary

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

The NM_004484.4(GPC3):c.337+21311T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 111,578 control chromosomes in the GnomAD database, including 1,140 homozygotes. There are 5,042 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 0.14 (1140 hom., 5042 hem., cov: 22)
• Consequence: GPC3 NM_004484.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.240

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPC3	NM_004484.4	c.337+21311T>C		intron_variant		ENST00000370818.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPC3	ENST00000370818.8	c.337+21311T>C		intron_variant		1	NM_004484.4	P1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 15956 AN: 111528 Hom.: 1137 Cov.: 22 AF XY: 0.149 AC XY: 5036 AN XY: 33722

Gnomad AFR AF: 0.0853

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.0920

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.0672

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.143 AC: 15970 AN: 111578 Hom.: 1140 Cov.: 22 AF XY: 0.149 AC XY: 5042 AN XY: 33782

Gnomad4 AFR AF: 0.0854

Gnomad4 AMR AF: 0.361

Gnomad4 ASJ AF: 0.0920

Gnomad4 EAS AF: 0.430

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.157

Alfa AF: 0.135 Hom.: 6938

Bravo AF: 0.167

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	4.9
Dann	Benign	0.57

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: rs1264379; hg19: chrX-133065766;