Genetic Variant PCTP:p.Arg120Trp (chr17-55773742-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_021213.4(PCTP):c.358C>T(p.Arg120Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000471 in 1,612,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

PCTP
NM_021213.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.76

Publications

1 publications found

Variant links:

Genes affected

PCTP (HGNC:8752): (phosphatidylcholine transfer protein) Enables phosphatidylcholine binding activity and phosphatidylcholine transporter activity. Involved in phospholipid transport. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

PCTP links:

Genome browser will be placed here

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;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCTP	NM_021213.4 link	c.358C>T	p.Arg120Trp	missense_variant	Exon 4 of 6	ENST00000268896.10	NP_067036.2	Q9UKL6-1Q549N3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCTP	ENST00000268896.10 link	c.358C>T	p.Arg120Trp	missense_variant	Exon 4 of 6	1	NM_021213.4	ENSP00000268896.4		Q9UKL6-1

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000479

AC:

AN:

250476

AF XY:

0.0000665

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000698

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000442

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000479

AC:

AN:

1460656

Hom.:

Cov.:

AF XY:

0.0000564

AC XY:

AN XY:

726420

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33468

American (AMR)

AF:

0.00

AC:

AN:

44670

Ashkenazi Jewish (ASJ)

AF:

0.000690

AC:

AN:

26104

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86134

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53372

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.0000423

AC:

AN:

1111184

Other (OTH)

AF:

0.0000497

AC:

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000395

AC:

AN:

152090

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41400

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000132

Hom.:

Bravo

AF:

0.0000718

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 28, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.358C>T (p.R120W) alteration is located in exon 4 (coding exon 4) of the PCTP gene. This alteration results from a C to T substitution at nucleotide position 358, causing the arginine (R) at amino acid position 120 to be replaced by a tryptophan (W). 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

0.18

BayesDel_addAF

Benign

-0.026

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.35

T;T;T;.;T

Eigen

Benign

0.033

Eigen_PC

Benign

0.069

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.82

T;T;T;T;D

M_CAP

Benign

0.048

MetaRNN

Benign

0.30

T;T;T;T;T

MetaSVM

Benign

-0.46

MutationAssessor

Uncertain

2.9

M;.;.;.;.

PhyloP100

1.8

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-3.7

D;.;.;.;.

REVEL

Uncertain

0.45

Sift

Benign

0.19

T;.;.;.;.

Sift4G

Benign

0.18

T;T;T;T;D

Polyphen

0.52

P;.;.;.;.

Vest4

0.34

MVP

0.85

MPC

0.080

ClinPred

0.33

GERP RS

4.9

PromoterAI

0.0072

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.23

gMVP

0.67

Mutation Taster

=47/53

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.28

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.28

Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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17-55773742-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over