Genetic Variant NM_002081.3:c.88C>T (chr2-240436006-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002081.3(GPC1):c.88C>T(p.Arg30Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000731 in 1,231,558 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R30Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000073 ( 0 hom. )

Consequence

GPC1
NM_002081.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.381

Publications

1 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002081.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPC1	NM_002081.3	MANE Select	c.88C>T	p.Arg30Trp	missense	Exon 1 of 9	NP_002072.2	A0A384NPH9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPC1	ENST00000264039.7	TSL:1 MANE Select	c.88C>T	p.Arg30Trp	missense	Exon 1 of 9	ENSP00000264039.2	P35052-1
GPC1	ENST00000943307.1		c.88C>T	p.Arg30Trp	missense	Exon 1 of 10	ENSP00000613366.1
GPC1	ENST00000943308.1		c.88C>T	p.Arg30Trp	missense	Exon 1 of 9	ENSP00000613367.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000314

AC:

AN:

95652

AF XY:

0.0000177

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000248

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000731

AC:

AN:

1231558

Hom.:

Cov.:

AF XY:

0.00000663

AC XY:

AN XY:

603628

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25842

American (AMR)

AF:

0.000138

AC:

AN:

21738

Ashkenazi Jewish (ASJ)

AF:

0.0000493

AC:

AN:

20278

East Asian (EAS)

AF:

0.00

AC:

AN:

29084

South Asian (SAS)

AF:

0.00

AC:

AN:

53934

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29846

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3428

European-Non Finnish (NFE)

AF:

0.00000501

AC:

AN:

998082

Other (OTH)

AF:

0.00

AC:

AN:

49326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.414

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000876

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.36

Eigen

Benign

0.15

Eigen_PC

Benign

-0.051

FATHMM_MKL

Benign

0.24

LIST_S2

Uncertain

0.92

M_CAP

Pathogenic

0.91

MetaRNN

Uncertain

0.52

MetaSVM

Benign

-0.41

MutationAssessor

Uncertain

2.8

PhyloP100

-0.38

PrimateAI

Pathogenic

0.95

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.17

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.18

MutPred

0.66

Loss of disorder (P = 0.0067)

MVP

0.91

MPC

0.64

ClinPred

0.74

GERP RS

1.5

PromoterAI

-0.043

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.64

gMVP

0.64

Mutation Taster

=65/35

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over