rs781197401

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_013363.4(PCOLCE2):​c.401G>T​(p.Gly134Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PCOLCE2
NM_013363.4 missense

Scores

8
7
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.39
Variant links:
Genes affected
PCOLCE2 (HGNC:8739): (procollagen C-endopeptidase enhancer 2) Enables collagen binding activity; heparin binding activity; and peptidase activator activity. Predicted to be involved in positive regulation of peptidase activity. Predicted to act upstream of or within cellular response to leukemia inhibitory factor. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.856

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PCOLCE2NM_013363.4 linkc.401G>T p.Gly134Val missense_variant Exon 3 of 9 ENST00000295992.8 NP_037495.1 Q9UKZ9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PCOLCE2ENST00000295992.8 linkc.401G>T p.Gly134Val missense_variant Exon 3 of 9 1 NM_013363.4 ENSP00000295992.3 Q9UKZ9

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461856
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727230
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.96
BayesDel_addAF
Pathogenic
0.24
D
BayesDel_noAF
Uncertain
0.10
CADD
Pathogenic
29
DANN
Uncertain
0.99
DEOGEN2
Benign
0.21
T;.;T
Eigen
Pathogenic
0.91
Eigen_PC
Pathogenic
0.86
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.95
D;D;D
M_CAP
Benign
0.054
D
MetaRNN
Pathogenic
0.86
D;D;D
MetaSVM
Benign
-0.74
T
MutationAssessor
Pathogenic
3.1
M;.;.
PrimateAI
Uncertain
0.78
T
PROVEAN
Pathogenic
-6.8
D;.;D
REVEL
Uncertain
0.59
Sift
Uncertain
0.0040
D;.;T
Sift4G
Uncertain
0.0060
D;.;D
Polyphen
0.99
D;.;.
Vest4
0.98
MutPred
0.65
Loss of disorder (P = 0.034);Loss of disorder (P = 0.034);Loss of disorder (P = 0.034);
MVP
0.49
MPC
0.70
ClinPred
0.99
D
GERP RS
5.3
Varity_R
0.83
gMVP
0.74

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-142567106; API