17-55773836-G-A

Variant names:

• chr17-55773836-G-A
• rs762655094
• NM_021213.4:c.452G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_021213.4(PCTP):​c.452G>A​(p.Arg151Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,612,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R151W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: PCTP NM_021213.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.42
• Publications: 3 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.901

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCTP	NM_021213.4	c.452G>A	p.Arg151Gln	missense_variant	Exon 4 of 6	ENST00000268896.10	NP_067036.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCTP	ENST00000268896.10	c.452G>A	p.Arg151Gln	missense_variant	Exon 4 of 6	1	NM_021213.4	ENSP00000268896.4

Frequencies

GnomAD3 genomes AF: 0.0000461 AC: 7 AN: 151978 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000200 AC: 5 AN: 249510 AF XY: 0.0000222

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000580

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000890 AC: 13 AN: 1460954 Hom.: 0 Cov.: 57 AF XY: 0.0000124 AC XY: 9 AN XY: 726670

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.0000448 AC: 2 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26118

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39656

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86160

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53130

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111606

Other (OTH) AF: 0.00 AC: 0 AN: 60366

GnomAD4 genome AF: 0.0000461 AC: 7 AN: 151978 Hom.: 0 Cov.: 30 AF XY: 0.0000674 AC XY: 5 AN XY: 74232

African (AFR) AF: 0.0000725 AC: 3 AN: 41364

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67980

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000330 Hom.: 0

Bravo AF: 0.0000453

ExAC AF: 0.0000247 AC: 3

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 05, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.452G>A (p.R151Q) alteration is located in exon 4 (coding exon 4) of the PCTP gene. This alteration results from a G to A substitution at nucleotide position 452, causing the arginine (R) at amino acid position 151 to be replaced by a glutamine (Q). 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	Uncertain	0.45
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.42
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.74	D;T;T;.;T
Eigen	Pathogenic	0.95
Eigen_PC	Pathogenic	0.89
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	D;D;D;D;D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.90	D;D;D;D;D
MetaSVM	Pathogenic	0.94	D
MutationAssessor	Pathogenic	3.2	M;.;.;.;.
PhyloP100		7.4
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-3.7	D;.;.;.;.
REVEL	Pathogenic	0.88
Sift	Uncertain	0.023	D;.;.;.;.
Sift4G	Pathogenic	0.0	D;D;D;D;D
Polyphen		1.0	D;.;.;.;.
Vest4		0.98
MVP		0.93
MPC		0.46
ClinPred		0.98	D
GERP RS		5.9
PromoterAI		-0.057	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.89
gMVP		0.77
Mutation Taster		=33/67	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs762655094; hg19: chr17-53851197;