Variant 17-67532908-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_012417.4(PITPNC1):c.155A>G(p.His52Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,902 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Consequence

PITPNC1
NM_012417.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.32

Variant links:

Genes affected

PITPNC1 (HGNC:21045): (phosphatidylinositol transfer protein cytoplasmic 1) This gene encodes a member of the phosphatidylinositol transfer protein family. The encoded cytoplasmic protein plays a role in multiple processes including cell signaling and lipid metabolism by facilitating the transfer of phosphatidylinositol between membrane compartments. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 1. [provided by RefSeq, May 2012]

PITPNC1 links:

PITPNC1 (HGNC:):

PITPNC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PITPNC1	NM_012417.4 linkuse as main transcript	c.155A>G	p.His52Arg	missense_variant	2/9	ENST00000581322.6	NP_036549.2	Q9UKF7-1
PITPNC1	NM_181671.3 linkuse as main transcript	c.155A>G	p.His52Arg	missense_variant	2/10		NP_858057.1	Q9UKF7A0A0C4DGP0
PITPNC1	XM_047435746.1 linkuse as main transcript	c.86A>G	p.His29Arg	missense_variant	2/9		XP_047291702.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PITPNC1	ENST00000581322.6 linkuse as main transcript	c.155A>G	p.His52Arg	missense_variant	2/9	1	NM_012417.4	ENSP00000464006.1		Q9UKF7-1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151902

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151902

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74172

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 31, 2024

The c.155A>G (p.H52R) alteration is located in exon 2 (coding exon 2) of the PITPNC1 gene. This alteration results from a A to G substitution at nucleotide position 155, causing the histidine (H) at amino acid position 52 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

Benign

0.29

BayesDel_addAF

Benign

-0.032

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Benign

0.95

DEOGEN2

Benign

0.099

.;T;T;T;T

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.93

D;D;D;D;D

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.50

D;D;D;D;D

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.4

.;.;M;.;.

PrimateAI

Uncertain

0.76

PROVEAN

Pathogenic

-6.4

D;.;.;.;.

REVEL

Uncertain

0.30

Sift

Benign

0.35

T;.;.;.;.

Sift4G

Benign

0.19

T;T;T;D;D

Polyphen

0.22

.;.;B;.;.

Vest4

0.55

MutPred

0.48

Gain of MoRF binding (P = 0.0967);Gain of MoRF binding (P = 0.0967);Gain of MoRF binding (P = 0.0967);.;.;

MVP

0.34

MPC

1.0

ClinPred

0.86

GERP RS

5.8

Varity_R

0.57

gMVP

0.96

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over