rs1256643378

Variant names:

• chrX-133303069-C-G
• NM_001448.3:c.1469G>C

Your query was ambiguous. Multiple possible variants found:

• chrX-133303069-C-G
• chrX-133303069-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001448.3(GPC4):​c.1469G>C​(p.Ser490Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000912 in 1,096,888 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. S490N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
• Consequence: GPC4 NM_001448.3 missense, splice_region
• Scores: Splicing: ADA: 0.8803
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.924

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2578844).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPC4	NM_001448.3	c.1469G>C	p.Ser490Thr	missense_variant, splice_region_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.1469G>C	p.Ser490Thr	missense_variant, splice_region_variant	Exon 9 of 9	1	NM_001448.3	ENSP00000359864.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.12e-7 AC: 1 AN: 1096888 Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 1 AN XY: 362344

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.8	M
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.24
Sift	Uncertain	0.022	D
Sift4G	Uncertain	0.035	D
Polyphen		0.88	P
Vest4		0.078
MutPred		0.59		Loss of disorder (P = 0.0543);
MVP		0.39
MPC		0.77
ClinPred		0.91	D
GERP RS		3.8
Varity_R		0.16
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.88
dbscSNV1_RF	Benign	0.67
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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-132437097;