13-91693403-C-T

Variant summary

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

The NM_004466.6(GPC5):​c.542C>T​(p.Pro181Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

GPC5
NM_004466.6 missense

Scores

2
11
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.14
Variant links:
Genes affected
GPC5 (HGNC:4453): (glypican 5) 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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GPC5NM_004466.6 linkc.542C>T p.Pro181Leu missense_variant Exon 3 of 8 ENST00000377067.9 NP_004457.1 P78333

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GPC5ENST00000377067.9 linkc.542C>T p.Pro181Leu missense_variant Exon 3 of 8 1 NM_004466.6 ENSP00000366267.3 P78333

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 14, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.542C>T (p.P181L) alteration is located in exon 3 (coding exon 3) of the GPC5 gene. This alteration results from a C to T substitution at nucleotide position 542, causing the proline (P) at amino acid position 181 to be replaced by a leucine (L). 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
0.16
BayesDel_addAF
Uncertain
0.045
T
BayesDel_noAF
Benign
-0.17
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.44
T;.
Eigen
Uncertain
0.45
Eigen_PC
Uncertain
0.46
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.91
D;D
M_CAP
Benign
0.054
D
MetaRNN
Uncertain
0.74
D;D
MetaSVM
Benign
-0.59
T
MutationAssessor
Uncertain
2.3
M;.
PrimateAI
Uncertain
0.56
T
PROVEAN
Pathogenic
-8.3
D;.
REVEL
Uncertain
0.35
Sift
Benign
0.031
D;.
Sift4G
Uncertain
0.0020
D;D
Polyphen
0.68
P;.
Vest4
0.61
MutPred
0.61
Gain of catalytic residue at V183 (P = 0.001);.;
MVP
0.27
MPC
0.22
ClinPred
1.0
D
GERP RS
5.1
Varity_R
0.60
gMVP
0.65

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: rs2035802337; hg19: chr13-92345657; API