rs148166792

Variant names:

• chrX-133302940-C-G
• rs148166792
• NM_001448.3:c.1598G>C

Your query was ambiguous. Multiple possible variants found:

• chrX-133302940-C-G
• chrX-133302940-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001448.3(GPC4):​c.1598G>C​(p.Arg533Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R533C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 24)
• Consequence: GPC4 NM_001448.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

Genes affected

GPC4 (HGNC:4452): (glypican 4) 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 GPC4 gene is adjacent to the 3' end of GPC3 and may also play a role in Simpson-Golabi-Behmel syndrome. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058105588).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPC4	NM_001448.3	c.1598G>C	p.Arg533Pro	missense_variant	Exon 9 of 9	ENST00000370828.4	NP_001439.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPC4	ENST00000370828.4	c.1598G>C	p.Arg533Pro	missense_variant	Exon 9 of 9	1	NM_001448.3	ENSP00000359864.3

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.26
DANN	Benign	0.70
DEOGEN2	Benign	0.14	T
FATHMM_MKL	Benign	0.092	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.065
Sift	Benign	0.37	T
Sift4G	Benign	0.29	T
Polyphen		0.0	B
Vest4		0.075
MutPred		0.47		Gain of helix (P = 0.0325);
MVP		0.043
MPC		0.79
ClinPred		0.039	T
GERP RS		-2.9
Varity_R		0.13
gMVP		0.43

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: rs148166792; hg19: chrX-132436968; COSMIC: COSV100895478;