2-240462244-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002081.3(GPC1):​c.379C>T​(p.Pro127Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000133 in 1,610,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P127P) has been classified as Benign.

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

GPC1
NM_002081.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.276
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.07942513).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GPC1NM_002081.3 linkc.379C>T p.Pro127Ser missense_variant Exon 3 of 9 ENST00000264039.7 NP_002072.2 P35052-1A0A384NPH9
GPC1XM_047443961.1 linkc.163C>T p.Pro55Ser missense_variant Exon 3 of 9 XP_047299917.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GPC1ENST00000264039.7 linkc.379C>T p.Pro127Ser missense_variant Exon 3 of 9 1 NM_002081.3 ENSP00000264039.2 P35052-1

Frequencies

GnomAD3 genomes
AF:
0.000125
AC:
19
AN:
152220
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000206
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000615
AC:
15
AN:
243788
Hom.:
0
AF XY:
0.0000602
AC XY:
8
AN XY:
132972
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.000137
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000134
AC:
195
AN:
1458360
Hom.:
0
Cov.:
33
AF XY:
0.000108
AC XY:
78
AN XY:
725198
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.000173
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.000125
AC:
19
AN:
152338
Hom.:
0
Cov.:
33
AF XY:
0.000148
AC XY:
11
AN XY:
74498
show subpopulations
Gnomad4 AFR
AF:
0.000120
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000206
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000214
Hom.:
0
Bravo
AF:
0.000151
ESP6500AA
AF:
0.000228
AC:
1
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.0000579
AC:
7
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000595

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 17, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.379C>T (p.P127S) alteration is located in exon 3 (coding exon 3) of the GPC1 gene. This alteration results from a C to T substitution at nucleotide position 379, causing the proline (P) at amino acid position 127 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.29
CADD
Benign
19
DANN
Benign
0.33
DEOGEN2
Benign
0.13
T;T;.;.;T
Eigen
Benign
-0.74
Eigen_PC
Benign
-0.74
FATHMM_MKL
Benign
0.14
N
LIST_S2
Benign
0.72
T;T;T;T;T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.079
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.2
L;.;.;.;.
PrimateAI
Benign
0.46
T
PROVEAN
Uncertain
-3.4
D;.;D;.;.
REVEL
Benign
0.20
Sift
Benign
0.81
T;.;T;.;.
Sift4G
Benign
0.76
T;T;T;T;T
Polyphen
0.0020
B;.;.;.;.
Vest4
0.27
MVP
0.67
MPC
0.27
ClinPred
0.055
T
GERP RS
3.1
Varity_R
0.30
gMVP
0.25

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

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

Other links and lift over

dbSNP: rs150046174; hg19: chr2-241401661; API