chr17-1553034-T-C

Position:

• chr17-1553034-T-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_006224.4(PITPNA):​c.167A>G​(p.Gln56Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PITPNA NM_006224.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.81

Genes affected

PITPNA (HGNC:9001): (phosphatidylinositol transfer protein alpha) This gene encodes a member of a family of lipid-binding proteins that transfer molecules of phosphatidylinositol or phosphatidylcholine between membrane surfaces. The protein is implicated in phospholipase C signaling and in the production of phosphatidylinositol 3,4,5-trisphosphate (PIP3) by phosphoinositide-3-kinase.[provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.979

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PITPNA	NM_006224.4	c.167A>G	p.Gln56Arg	missense_variant	3/12	ENST00000313486.12	NP_006215.1
PITPNA	XM_047436299.1	c.-53A>G		5_prime_UTR_variant	3/12		XP_047292255.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PITPNA	ENST00000313486.12	c.167A>G	p.Gln56Arg	missense_variant	3/12	5	NM_006224.4	ENSP00000316809.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 29, 2024

The c.167A>G (p.Q56R) alteration is located in exon 3 (coding exon 3) of the PITPNA gene. This alteration results from a A to G substitution at nucleotide position 167, causing the glutamine (Q) at amino acid position 56 to be replaced by an arginine (R). 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	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.26
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	T;.;T
Eigen	Pathogenic	0.97
Eigen_PC	Pathogenic	0.93
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D;D;D
M_CAP	Benign	0.041	D
MetaRNN	Pathogenic	0.98	D;D;D
MetaSVM	Uncertain	0.052	D
MutationAssessor	Pathogenic	4.2	H;.;.
PROVEAN	Uncertain	-3.5	D;D;.
REVEL	Uncertain	0.62
Sift	Pathogenic	0.0	D;D;.
Sift4G	Uncertain	0.027	D;D;D
Polyphen		0.99	D;.;.
Vest4		0.87
MutPred		0.94		Gain of MoRF binding (P = 0.0196);Gain of MoRF binding (P = 0.0196);.;
MVP		0.79
MPC		2.1
ClinPred		1.0	D
GERP RS		6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.86
gMVP		1.0

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-1456328;