Variant chr12-122986214-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_020845.3(PITPNM2):c.3863G>A(p.Arg1288His) variant causes a missense change. The variant allele was found at a frequency of 0.00081 in 1,562,640 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00084 ( 2 hom. )

Consequence

PITPNM2
NM_020845.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.12

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.028978914).

BS2

High AC in GnomAd4 at 81 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PITPNM2	NM_020845.3 linkuse as main transcript	c.3863G>A	p.Arg1288His	missense_variant	26/26	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.3863G>A	p.Arg1288His	missense_variant	26/26	5	NM_020845.3	ENSP00000322218	P3	Q9BZ72-1
PITPNM2	ENST00000280562.9 linkuse as main transcript	c.3845G>A	p.Arg1282His	missense_variant	25/25	5		ENSP00000280562	A2	Q9BZ72-2

Frequencies

GnomAD3 genomes

AF:

0.000532

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000926

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000446

AC:

AN:

161302

Hom.:

AF XY:

0.000417

AC XY:

AN XY:

88728

show subpopulations

Gnomad AFR exome

AF:

0.000111

Gnomad AMR exome

AF:

0.000191

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000773

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000900

Gnomad NFE exome

AF:

0.000834

Gnomad OTH exome

AF:

0.000224

GnomAD4 exome

AF:

0.000839

AC:

1184

AN:

1410422

Hom.:

Cov.:

AF XY:

0.000775

AC XY:

541

AN XY:

698246

show subpopulations

Gnomad4 AFR exome

AF:

0.0000306

Gnomad4 AMR exome

AF:

0.000160

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000266

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000578

Gnomad4 NFE exome

AF:

0.00103

Gnomad4 OTH exome

AF:

0.000460

GnomAD4 genome

AF:

0.000532

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.000484

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000941

Gnomad4 NFE

AF:

0.000926

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000689

Hom.:

Bravo

AF:

0.000442

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000606

AC:

ExAC

AF:

0.000252

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

May 21, 2024

The c.3863G>A (p.R1288H) alteration is located in exon 25 (coding exon 24) of the PITPNM2 gene. This alteration results from a G to A substitution at nucleotide position 3863, causing the arginine (R) at amino acid position 1288 to be replaced by a histidine (H). 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

Uncertain

0.40

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Uncertain

0.010

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.59

D;.;D

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.97

.;D;D

M_CAP

Benign

0.052

MetaRNN

Benign

0.029

T;T;T

MetaSVM

Benign

-0.36

MutationAssessor

Uncertain

2.9

M;.;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-3.5

D;D;D

REVEL

Uncertain

0.44

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.0080

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.57

MVP

0.33

MPC

2.4

ClinPred

0.31

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.39

gMVP

0.42

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