Variant chr12-122987336-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_020845.3(PITPNM2):c.3358G>A(p.Val1120Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000285 in 1,612,570 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000098 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

PITPNM2
NM_020845.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.90

Variant links:

Genes affected

PITPNM2 (HGNC:21044): (phosphatidylinositol transfer protein membrane associated 2) PITPNM2 belongs to a family of membrane-associated phosphatidylinositol transfer domain-containing proteins that share homology with the Drosophila retinal degeneration B (rdgB) protein (Ocaka et al., 2005 [PubMed 15627748]).[supplied by OMIM, Mar 2008]

PITPNM2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 15 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PITPNM2	NM_020845.3 linkuse as main transcript	c.3358G>A	p.Val1120Met	missense_variant	23/26	ENST00000320201.10	NP_065896.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PITPNM2	ENST00000320201.10 linkuse as main transcript	c.3358G>A	p.Val1120Met	missense_variant	23/26	5	NM_020845.3	ENSP00000322218	P3	Q9BZ72-1
PITPNM2	ENST00000280562.9 linkuse as main transcript	c.3340G>A	p.Val1114Met	missense_variant	22/25	5		ENSP00000280562	A2	Q9BZ72-2

Frequencies

GnomAD3 genomes

AF:

0.0000985

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000359

AC:

AN:

250906

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135776

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000212

AC:

AN:

1460222

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

726478

show subpopulations

Gnomad4 AFR exome

AF:

0.000359

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.0000985

AC:

AN:

152348

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.000166

ExAC

AF:

0.0000330

AC:

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

Dec 16, 2022

The c.3358G>A (p.V1120M) alteration is located in exon 22 (coding exon 21) of the PITPNM2 gene. This alteration results from a G to A substitution at nucleotide position 3358, causing the valine (V) at amino acid position 1120 to be replaced by a methionine (M). 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

0.99

BayesDel_addAF

Benign

-0.0078

BayesDel_noAF

Uncertain

0.030

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

T;.;T

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

.;D;D

M_CAP

Uncertain

0.095

MetaRNN

Uncertain

0.60

D;D;D

MetaSVM

Uncertain

0.13

MutationAssessor

Uncertain

2.2

M;.;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-1.7

N;N;N

REVEL

Uncertain

0.53

Sift

Benign

0.19

T;T;T

Sift4G

Benign

0.079

T;T;T

Polyphen

1.0

D;D;D

Vest4

0.82

MVP

0.47

MPC

2.2

ClinPred

0.42

GERP RS

4.8

Varity_R

0.18

gMVP

0.84

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