chrX-133535890-TTTTC-T

Variant names:

• chrX-133535890-TTTTC-T
• rs71736291
• NM_004484.4:c.*230_*233delGAAA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_004484.4(GPC3):​c.*230_*233delGAAA 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 0 publications found

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]

GPC3 Gene-Disease associations (from GenCC):

• Simpson-Golabi-Behmel syndrome

  Inheritance: XL Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Simpson-Golabi-Behmel syndrome type 1

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• 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 rank	MANE	Protein	UniProt
GPC3	NM_004484.4	c.*230_*233delGAAA		3_prime_UTR_variant	Exon 8 of 8	ENST00000370818.8	NP_004475.1
GPC3	NM_001164617.2	c.*230_*233delGAAA		3_prime_UTR_variant	Exon 9 of 9		NP_001158089.1
GPC3	NM_001164618.2	c.*230_*233delGAAA		3_prime_UTR_variant	Exon 8 of 8		NP_001158090.1
GPC3	NM_001164619.2	c.*230_*233delGAAA		3_prime_UTR_variant	Exon 7 of 7		NP_001158091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPC3	ENST00000370818.8	c.*230_*233delGAAA		3_prime_UTR_variant	Exon 8 of 8	1	NM_004484.4	ENSP00000359854.3

Frequencies

GnomAD3 genomes AF: 0.0520 AC: 5712 AN: 109894 Hom.: 411 Cov.: 20

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

African (AFR) AF: 0.189 AC: 1683 AN: 8902

American (AMR) AF: 0.0127 AC: 145 AN: 11442

Ashkenazi Jewish (ASJ) AF: 0.00599 AC: 53 AN: 8846

East Asian (EAS) AF: 0.00 AC: 0 AN: 21638

South Asian (SAS) AF: 0.000265 AC: 4 AN: 15115

European-Finnish (FIN) AF: 0.0000517 AC: 1 AN: 19350

Middle Eastern (MID) AF: 0.00921 AC: 11 AN: 1194

European-Non Finnish (NFE) AF: 0.000355 AC: 60 AN: 169196

Other (OTH) AF: 0.0166 AC: 283 AN: 17074

GnomAD4 genome AF: 0.0521 AC: 5726 AN: 109937 Hom.: 413 Cov.: 20 AF XY: 0.0416 AC XY: 1341 AN XY: 32253

African (AFR) AF: 0.180 AC: 5408 AN: 29980

American (AMR) AF: 0.0198 AC: 203 AN: 10266

Ashkenazi Jewish (ASJ) AF: 0.00723 AC: 19 AN: 2627

East Asian (EAS) AF: 0.00 AC: 0 AN: 3510

South Asian (SAS) AF: 0.000787 AC: 2 AN: 2541

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5858

Middle Eastern (MID) AF: 0.00465 AC: 1 AN: 215

European-Non Finnish (NFE) AF: 0.000587 AC: 31 AN: 52775

Other (OTH) AF: 0.0419 AC: 62 AN: 1479

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

Jul 03, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs71736291; hg19: chrX-132669918;