chr17-55773746-G-A

Variant names:

• chr17-55773746-G-A
• rs141170729
• NM_021213.4:c.362G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_021213.4(PCTP):​c.362G>A​(p.Arg121Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000775 in 1,613,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000084 (0 hom.)
• Consequence: PCTP NM_021213.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.429
• Publications: 0 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.280523).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCTP	NM_021213.4	c.362G>A	p.Arg121Gln	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.362G>A	p.Arg121Gln	missense_variant	Exon 4 of 6	1	NM_021213.4	ENSP00000268896.4

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152066 Hom.: 0 Cov.: 30

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000199 AC: 5 AN: 250708 AF XY: 0.0000221

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: 0.0000442

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000842 AC: 123 AN: 1461282 Hom.: 0 Cov.: 57 AF XY: 0.0000688 AC XY: 50 AN XY: 726838

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

American (AMR) AF: 0.00 AC: 0 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86192

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.000109 AC: 121 AN: 1111620

Other (OTH) AF: 0.0000331 AC: 2 AN: 60370

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152066 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 74270

African (AFR) AF: 0.00 AC: 0 AN: 41390

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68016

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

Alfa AF: 0.0000773 Hom.: 0

Bravo AF: 0.0000113

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.362G>A (p.R121Q) 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 362, causing the arginine (R) at amino acid position 121 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	Benign	0.085
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T;T;T;.;T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.42	N
LIST_S2	Uncertain	0.88	D;D;D;D;T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.28	T;T;T;T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.7	L;.;.;.;.
PhyloP100		0.43
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-3.1	D;.;.;.;.
REVEL	Uncertain	0.37
Sift	Benign	0.10	T;.;.;.;.
Sift4G	Benign	0.13	T;T;T;T;T
Polyphen		0.84	P;.;.;.;.
Vest4		0.11
MVP		0.78
MPC		0.097
ClinPred		0.57	D
GERP RS		0.44
PromoterAI		0.0090	Neutral
Varity_R		0.22
gMVP		0.50
Mutation Taster		=80/20	polymorphism

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

Other links and lift over

dbSNP: rs141170729; hg19: chr17-53851107;