rs138434031

Variant names:

• chr2-240459161-C-G
• rs138434031
• NM_002081.3:c.298C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-240459161-C-G
• chr2-240459161-C-T

Variant summary

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

The NM_002081.3(GPC1):​c.298C>G​(p.Leu100Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,072 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/22 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. L100F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GPC1 NM_002081.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.912
• Publications: 0 publications found

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]

ACMG classification

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.298C>G	p.Leu100Val	missense	Exon 2 of 9	NP_002072.2	A0A384NPH9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPC1	ENST00000264039.7	TSL:1 MANE Select	c.298C>G	p.Leu100Val	missense	Exon 2 of 9	ENSP00000264039.2	P35052-1
	GPC1	ENST00000495100.1	TSL:1	n.975C>G		non_coding_transcript_exon	Exon 1 of 7
	GPC1	ENST00000943307.1		c.298C>G	p.Leu100Val	missense	Exon 2 of 10	ENSP00000613366.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460072 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726382

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26084

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86194

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52102

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111772

Other (OTH) AF: 0.00 AC: 0 AN: 60334

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Benign	0.032
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.31	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		0.91
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.26
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.017	D
Polyphen		0.93	P
Vest4		0.47
MutPred		0.75		Gain of MoRF binding (P = 0.0937)
MVP		0.82
MPC		0.61
ClinPred		0.97	D
GERP RS		3.1
Varity_R		0.62
gMVP		0.56
Mutation Taster		=72/28	polymorphism

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: rs138434031; hg19: chr2-241398578;