X-133754180-TAAAAAA-TAAAAAAAAA

Variant names:

• chrX-133754180-T-TAAA
• NM_004484.4:c.338-7_338-5dupTTT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1

The NM_004484.4(GPC3):​c.338-7_338-5dupTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., 0 hem., cov: 19)
  • Exomes 𝑓: 0.00015 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: GPC3 NM_004484.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.883

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 -4 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000149 (129/866690) while in subpopulation AFR AF= 0.000244 (5/20488). AF 95% confidence interval is 0.000133. There are 0 homozygotes in gnomad4_exome. There are 0 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPC3	NM_004484.4	c.338-7_338-5dupTTT		splice_region_variant, intron_variant	Intron 2 of 7	ENST00000370818.8	NP_004475.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPC3	ENST00000370818.8	c.338-5_338-4insTTT		splice_region_variant, intron_variant	Intron 2 of 7	1	NM_004484.4	ENSP00000359854.3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 76507 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 17849 FAILED QC

Gnomad AFR AF: 0.00

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000149 AC: 129 AN: 866690 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 253910

Gnomad4 AFR exome AF: 0.000244

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.000235

Gnomad4 EAS exome AF: 0.000139

Gnomad4 SAS exome AF: 0.000113

Gnomad4 FIN exome AF: 0.0000302

Gnomad4 NFE exome AF: 0.000159

Gnomad4 OTH exome AF: 0.0000791

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 76507 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 17849

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-132888207;