Genetic Variant PCTP:p.Met173Ile (chr17-55774799-G-A) – 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.519G>A(p.Met173Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000107 in 1,595,110 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 27)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

PCTP
NM_021213.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.22

Publications

0 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.519G>A	p.Met173Ile	missense_variant	Exon 5 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.519G>A	p.Met173Ile	missense_variant	Exon 5 of 6	1	NM_021213.4	ENSP00000268896.4		Q9UKL6-1

Frequencies

GnomAD3 genomes

AF:

0.00000668

AC:

AN:

149712

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000159

AC:

AN:

251124

AF XY:

0.0000221

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000111

AC:

AN:

1445398

Hom.:

Cov.:

AF XY:

0.0000153

AC XY:

AN XY:

719140

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33034

American (AMR)

AF:

0.00

AC:

AN:

44280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25566

East Asian (EAS)

AF:

0.00

AC:

AN:

38266

South Asian (SAS)

AF:

0.00

AC:

AN:

86012

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52220

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5690

European-Non Finnish (NFE)

AF:

0.0000145

AC:

AN:

1100950

Other (OTH)

AF:

0.00

AC:

AN:

59380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000668

AC:

AN:

149712

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

72888

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40562

American (AMR)

AF:

0.00

AC:

AN:

14928

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

5058

South Asian (SAS)

AF:

0.00

AC:

AN:

4752

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10014

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67658

Other (OTH)

AF:

0.00

AC:

AN:

2062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000868

Hom.:

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

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

Dec 13, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.519G>A (p.M173I) alteration is located in exon 5 (coding exon 5) of the PCTP gene. This alteration results from a G to A substitution at nucleotide position 519, causing the methionine (M) at amino acid position 173 to be replaced by an isoleucine (I). 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

Pathogenic

0.73

BayesDel_addAF

Benign

-0.046

BayesDel_noAF

Benign

-0.20

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.42

T;T;T;.;T

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.87

D;D;D;D;D

M_CAP

Benign

0.026

MetaRNN

Uncertain

0.66

D;D;D;D;D

MetaSVM

Benign

-0.58

MutationAssessor

Uncertain

2.1

M;.;.;.;.

PhyloP100

6.2

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.5

D;.;.;.;.

REVEL

Uncertain

0.43

Sift

Benign

0.11

T;.;.;.;.

Sift4G

Benign

0.17

T;T;T;T;T

Polyphen

0.76

P;.;.;.;.

Vest4

0.51

MutPred

0.67

Loss of disorder (P = 0.1245);Loss of disorder (P = 0.1245);Loss of disorder (P = 0.1245);.;.;

MVP

0.71

MPC

0.090

ClinPred

0.76

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.54

gMVP

0.55

Mutation Taster

=65/35

polymorphism

(source)

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

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17-55774799-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over