chr17-55774851-G-A

Variant names:

• chr17-55774851-G-A
• NM_021213.4:c.571G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_021213.4(PCTP):​c.571G>A​(p.Ala191Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PCTP NM_021213.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.42
• 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 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	c.571G>A	p.Ala191Thr	missense_variant	Exon 5 of 6	ENST00000268896.10	NP_067036.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCTP	ENST00000268896.10	c.571G>A	p.Ala191Thr	missense_variant	Exon 5 of 6	1	NM_021213.4	ENSP00000268896.4

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1053728 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 530124

African (AFR) AF: 0.00 AC: 0 AN: 23452

American (AMR) AF: 0.00 AC: 0 AN: 37802

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16796

East Asian (EAS) AF: 0.00 AC: 0 AN: 18692

South Asian (SAS) AF: 0.00 AC: 0 AN: 80170

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4102

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 798854

Other (OTH) AF: 0.00 AC: 0 AN: 39484

GnomAD4 genome Cov.: 25

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 27, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.571G>A (p.A191T) 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 571, causing the alanine (A) at amino acid position 191 to be replaced by a threonine (T). 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	0.36
BayesDel_addAF	Uncertain	0.091	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T;T;T;.;T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.86	D;D;D;D;T
M_CAP	Benign	0.073	D
MetaRNN	Uncertain	0.70	D;D;D;D;D
MetaSVM	Uncertain	-0.032	T
MutationAssessor	Uncertain	2.7	M;.;.;.;.
PhyloP100		4.4
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-2.9	D;.;.;.;.
REVEL	Uncertain	0.60
Sift	Uncertain	0.0080	D;.;.;.;.
Sift4G	Uncertain	0.026	D;D;D;T;D
Polyphen		0.99	D;.;.;.;.
Vest4		0.71
MutPred		0.64		Loss of MoRF binding (P = 0.1496);Loss of MoRF binding (P = 0.1496);Loss of MoRF binding (P = 0.1496);.;.;
MVP		0.89
MPC		0.20
ClinPred		0.97	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.42
gMVP		0.58

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

hg19: chr17-53852212;