rs1490568896

chrX-133754180-T-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_004484.4(GPC3):c.338-4A>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00025 (0 hom., 0 hem., cov: 18)
  • Exomes 𝑓: 0.000075 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: GPC3 NM_004484.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00007847
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.447

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant X-133754180-T-A is Benign according to our data. Variant chrX-133754180-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 476654.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPC3	NM_004484.4	c.338-4A>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000370818.8

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00 AC: 19 AN: 76423 Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0 AN XY: 17807 FAILED QC

Gnomad AFR AF: 0.000291

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000704

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000290

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000749 AC: 65 AN: 867494 Hom.: 0 Cov.: 17 AF XY: 0.00 AC XY: 0 AN XY: 254276

Gnomad4 AFR exome AF: 0.000439

Gnomad4 AMR exome AF: 0.0000746

Gnomad4 ASJ exome AF: 0.000176

Gnomad4 EAS exome AF: 0.000139

Gnomad4 SAS exome AF: 0.0000225

Gnomad4 FIN exome AF: 0.000483

Gnomad4 NFE exome AF: 0.0000366

Gnomad4 OTH exome AF: 0.000132

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000249 AC: 19 AN: 76414 Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0 AN XY: 17816

Gnomad4 AFR AF: 0.000291

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000704

Gnomad4 NFE AF: 0.000290

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Wilms tumor 1 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jul 21, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
Cadd	Benign	6.6
Dann	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000078
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.060		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: rs1490568896; hg19: chrX-132888207; COSMIC: COSV104685920; COSMIC: COSV104685920;