Genetic Variant PCTP:c.-2A>G (chr17-55767408-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM1BP4_ModerateBS2

The NM_021213.4(PCTP):c.215A>G(p.Tyr72Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000575 in 1,613,198 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0010 ( 6 hom., cov: 32)

Exomes 𝑓: 0.00053 ( 1 hom. )

Consequence

PCTP
NM_021213.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.70

Publications

3 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: Likely_benign. The variant received -4 ACMG points.

PM1

In a binding_site (size 0) in uniprot entity PPCT_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.26276523).

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCTP	NM_021213.4 link	c.215A>G	p.Tyr72Cys	missense_variant	Exon 2 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.215A>G	p.Tyr72Cys	missense_variant	Exon 2 of 6	1	NM_021213.4	ENSP00000268896.4		Q9UKL6-1

Frequencies

GnomAD3 genomes

AF:

0.00101

AC:

154

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.0943

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000779

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000501

AC:

126

AN:

251402

AF XY:

0.000530

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000521

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000765

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000529

AC:

773

AN:

1460890

Hom.:

Cov.:

AF XY:

0.000556

AC XY:

404

AN XY:

726838

show subpopulations

African (AFR)

AF:

0.000149

AC:

AN:

33456

American (AMR)

AF:

0.000514

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.000115

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.000661

AC:

AN:

86228

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53378

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000598

AC:

664

AN:

1111204

Other (OTH)

AF:

0.000348

AC:

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

105

140

175

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00101

AC:

154

AN:

152308

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41552

American (AMR)

AF:

0.000392

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00104

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000779

AC:

AN:

68032

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000634

Hom.:

Bravo

AF:

0.00125

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000535

AC:

EpiCase

AF:

0.000927

EpiControl

AF:

0.000948

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 13, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.215A>G (p.Y72C) alteration is located in exon 2 (coding exon 2) of the PCTP gene. This alteration results from a A to G substitution at nucleotide position 215, causing the tyrosine (Y) at amino acid position 72 to be replaced by a cysteine (C). 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

0.17

BayesDel_addAF

Uncertain

0.078

BayesDel_noAF

Pathogenic

0.26

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.61

D;T;T

Eigen

Uncertain

0.26

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.85

T;T;T

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.26

T;T;T

MetaSVM

Uncertain

-0.20

MutationAssessor

Uncertain

2.6

M;.;.

PhyloP100

4.7

PrimateAI

Uncertain

0.54

PROVEAN

Pathogenic

-7.2

D;.;.

REVEL

Pathogenic

0.67

Sift

Benign

0.062

T;.;.

Sift4G

Benign

0.078

T;T;T

Polyphen

0.99

D;.;.

Vest4

0.82

MVP

0.95

MPC

0.19

ClinPred

0.13

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.80

gMVP

0.74

Mutation Taster

=41/59

disease causing

(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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17-55767408-A-G

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