dbSNP rs565369538: GPC1:p.Arg80Gly (chr2-240459101-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002081.3(GPC1):c.238C>G(p.Arg80Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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. R80C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

GPC1
NM_002081.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.144

Variant links:

Genes affected

GPC1 (HGNC:4449): (glypican 1) 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. [provided by RefSeq, Jul 2008]

GPC1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2797432).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPC1	NM_002081.3 link	c.238C>G	p.Arg80Gly	missense_variant	Exon 2 of 9	ENST00000264039.7	NP_002072.2	P35052-1A0A384NPH9
GPC1	XM_047443961.1 link	c.22C>G	p.Arg8Gly	missense_variant	Exon 2 of 9		XP_047299917.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPC1	ENST00000264039.7 link	c.238C>G	p.Arg80Gly	missense_variant	Exon 2 of 9	1	NM_002081.3	ENSP00000264039.2		P35052-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248338

Hom.:

AF XY:

0.00000741

AC XY:

AN XY:

135012

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460436

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726538

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.38

T;T;.;.;T

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.76

T;T;T;T;T

M_CAP

Benign

0.029

MetaRNN

Benign

0.28

T;T;T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.3

M;.;.;.;.

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-3.9

D;N;D;.;.

REVEL

Benign

0.11

Sift

Benign

0.048

D;D;T;.;.

Sift4G

Benign

0.10

T;T;T;T;T

Polyphen

0.20

B;.;.;.;.

Vest4

0.43

MutPred

0.58

Loss of catalytic residue at R80 (P = 0.0665);.;.;.;.;

MVP

0.70

MPC

0.47

ClinPred

0.90

GERP RS

3.1

Varity_R

0.34

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over