rs5977910

Variant names:

• chrX-133767266-A-C
• rs5977910
• NM_004484.4:c.338-13090T>G

Your query was ambiguous. Multiple possible variants found:

• chrX-133767266-A-C
• chrX-133767266-A-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001164617.2(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_001164617.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.894
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164617.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPC3	NM_004484.4	MANE Select	c.338-13090T>G		intron	N/A	NP_004475.1
	GPC3	NM_001164617.2		c.338-13090T>G		intron	N/A	NP_001158089.1
	GPC3	NM_001164618.2		c.290-13090T>G		intron	N/A	NP_001158090.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPC3	ENST00000370818.8	TSL:1 MANE Select	c.338-13090T>G		intron	N/A	ENSP00000359854.3
	GPC3	ENST00000394299.7	TSL:1	c.338-13090T>G		intron	N/A	ENSP00000377836.2
	GPC3	ENST00000631057.2	TSL:1	c.176-13090T>G		intron	N/A	ENSP00000486325.1

Frequencies

GnomAD3 genomes AF: 0.967 AC: 107121 AN: 110829 Hom.: 36613 Cov.: 23

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

African (AFR) AF: 0.993 AC: 30327 AN: 30526

American (AMR) AF: 0.981 AC: 10183 AN: 10381

Ashkenazi Jewish (ASJ) AF: 0.979 AC: 2584 AN: 2640

East Asian (EAS) AF: 0.783 AC: 2758 AN: 3523

South Asian (SAS) AF: 0.837 AC: 2136 AN: 2553

European-Finnish (FIN) AF: 0.916 AC: 5354 AN: 5842

Middle Eastern (MID) AF: 0.991 AC: 215 AN: 217

European-Non Finnish (NFE) AF: 0.971 AC: 51504 AN: 53020

Other (OTH) AF: 0.968 AC: 1451 AN: 1499

Alfa AF: 0.971 Hom.: 64142

Bravo AF: 0.972

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.7
DANN	Benign	0.72
PhyloP100		0.89
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: rs5977910; hg19: chrX-132901293;