17-55751153-G-A

Variant names:

• chr17-55751153-G-A
• rs1013234176
• NM_021213.4:c.50G>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.50G>A​(p.Cys17Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000358 in 1,395,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C17F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: PCTP NM_021213.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.32
• 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=0.331213).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCTP	NM_021213.4	c.50G>A	p.Cys17Tyr	missense_variant	Exon 1 of 6	ENST00000268896.10	NP_067036.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCTP	ENST00000268896.10	c.50G>A	p.Cys17Tyr	missense_variant	Exon 1 of 6	1	NM_021213.4	ENSP00000268896.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000358 AC: 5 AN: 1395730 Hom.: 0 Cov.: 30 AF XY: 0.00000436 AC XY: 3 AN XY: 688280

African (AFR) AF: 0.0000317 AC: 1 AN: 31530

American (AMR) AF: 0.00 AC: 0 AN: 35528

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25116

East Asian (EAS) AF: 0.00 AC: 0 AN: 35708

South Asian (SAS) AF: 0.00 AC: 0 AN: 79052

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47434

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5462

European-Non Finnish (NFE) AF: 0.00000371 AC: 4 AN: 1078036

Other (OTH) AF: 0.00 AC: 0 AN: 57864

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.59	D;T;T
Eigen	Benign	0.15
Eigen_PC	Benign	0.10
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.82	T;T;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.33	T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.4	M;.;.
PhyloP100		2.3
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-5.4	D;.;.
REVEL	Uncertain	0.31
Sift	Uncertain	0.0030	D;.;.
Sift4G	Uncertain	0.015	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.27
MutPred		0.59		Gain of disorder (P = 0.128);Gain of disorder (P = 0.128);Gain of disorder (P = 0.128);
MVP		0.61
MPC		0.50
ClinPred		0.99	D
GERP RS		1.9
PromoterAI		0.086	Neutral
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
Varity_R		0.82
gMVP		0.67
Mutation Taster		=93/7	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: rs1013234176; hg19: chr17-53828514;