X-133535890-TTTTC-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.15

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 -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	HGVSp	Effect	#exon/exons	MANE	UniProt
GPC3	NM_004484.4	c.*230_*233del		3_prime_UTR_variant	8/8	ENST00000370818.8
GPC3	NM_001164617.2	c.*230_*233del		3_prime_UTR_variant	9/9
GPC3	NM_001164618.2	c.*230_*233del		3_prime_UTR_variant	8/8
GPC3	NM_001164619.2	c.*230_*233del		3_prime_UTR_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPC3	ENST00000370818.8	c.*230_*233del		3_prime_UTR_variant	8/8	1	NM_004484.4	P1
GPC3	ENST00000394299.7	c.*230_*233del		3_prime_UTR_variant	9/9	1
GPC3	ENST00000669691.1	n.1039_1042del		non_coding_transcript_exon_variant	6/6

Frequencies

GnomAD3 genomes AF: 0.0520 AC: 5712 AN: 109894 Hom.: 411 Cov.: 20 AF XY: 0.0413 AC XY: 1331 AN XY: 32200

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

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.: 20 AF XY: 0.0416 AC XY: 1341 AN XY: 32253

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: 29 AN: 2518

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs71736291; hg19: chrX-132669918;