rs5977910

chrX-133767266-A-CchrX-133767266-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_004484.4(GPC3):c.338-13090T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.97 (36604 hom., 31756 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: GPC3 NM_004484.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.894

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BS2: High Homozygotes in GnomAd at 36613 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPC3	NM_004484.4	c.338-13090T>G		intron_variant		ENST00000370818.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPC3	ENST00000370818.8	c.338-13090T>G		intron_variant		1	NM_004484.4	P1

Frequencies

GnomAD3 genomes AF: 0.967 AC: 107121 AN: 110829 Hom.: 36613 Cov.: 23 AF XY: 0.961 AC XY: 31697 AN XY: 32995

Gnomad AFR AF: 0.993

Gnomad AMI AF: 0.960

Gnomad AMR AF: 0.981

Gnomad ASJ AF: 0.979

Gnomad EAS AF: 0.782

Gnomad SAS AF: 0.838

Gnomad FIN AF: 0.916

Gnomad MID AF: 0.992

Gnomad NFE AF: 0.971

Gnomad OTH AF: 0.974

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.966 AC: 107164 AN: 110880 Hom.: 36604 Cov.: 23 AF XY: 0.961 AC XY: 31756 AN XY: 33056

Gnomad4 AFR AF: 0.993

Gnomad4 AMR AF: 0.981

Gnomad4 ASJ AF: 0.979

Gnomad4 EAS AF: 0.783

Gnomad4 SAS AF: 0.837

Gnomad4 FIN AF: 0.916

Gnomad4 NFE AF: 0.971

Gnomad4 OTH AF: 0.968

Alfa AF: 0.970 Hom.: 50721

Bravo AF: 0.972

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	2.7
Dann	Benign	0.72

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: rs5977910; hg19: chrX-132901293;