17-67692697-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM2BP4_Strong

The NM_012417.4(PITPNC1):c.808A>G(p.Ser270Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000725 in 1,613,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000077 ( 0 hom. )

Consequence

PITPNC1
NM_012417.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.22

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:

LOC101928045 (HGNC:):

LOC101928045 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity PITC1_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.041391283).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PITPNC1	NM_012417.4 linkuse as main transcript	c.808A>G	p.Ser270Gly	missense_variant	9/9	ENST00000581322.6
LOC101928045	XR_002958126.2 linkuse as main transcript	n.229-3324T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PITPNC1	ENST00000581322.6 linkuse as main transcript	c.808A>G	p.Ser270Gly	missense_variant	9/9	1	NM_012417.4		Q9UKF7-1
PITPNC1	ENST00000580974.6 linkuse as main transcript	c.*120A>G		3_prime_UTR_variant	10/10	1		P1
PITPNC1	ENST00000578527.1 linkuse as main transcript	n.1065A>G		non_coding_transcript_exon_variant	7/7	1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152074

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:

0.00

Gnomad SAS

AF:

0.000624

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000124

AC:

AN:

249254

Hom.:

AF XY:

0.000192

AC XY:

AN XY:

135224

show subpopulations

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 SAS exome

AF:

0.000915

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000766

AC:

112

AN:

1461632

Hom.:

Cov.:

AF XY:

0.000109

AC XY:

AN XY:

727112

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000904

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000171

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152074

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000624

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000554

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.000116

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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

Nov 09, 2023

The c.808A>G (p.S270G) alteration is located in exon 9 (coding exon 9) of the PITPNC1 gene. This alteration results from a A to G substitution at nucleotide position 808, causing the serine (S) at amino acid position 270 to be replaced by a glycine (G). 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

0.063

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.49

Cadd

Benign

Dann

Benign

0.96

DEOGEN2

Benign

0.013

Eigen

Benign

-0.18

Eigen_PC

Benign

0.036

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.79

M_CAP

Benign

0.0072

MetaRNN

Benign

0.041

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

MutationTaster

Benign

0.99

D;D;D;D

PrimateAI

Benign

0.47

Sift4G

Benign

0.31

Polyphen

0.0

Vest4

0.17

MutPred

0.20

Loss of phosphorylation at S270 (P = 0.0046);

MVP

0.15

MPC

0.59

ClinPred

0.12

GERP RS

5.8

Varity_R

0.10

gMVP

0.50

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