rs28493751

Positions:

chr17-6538056-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_031220.4(PITPNM3):c.49C>T(p.Pro17Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0919 in 1,612,570 control chromosomes in the GnomAD database, including 7,452 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.082 ( 598 hom., cov: 32)

Exomes 𝑓: 0.093 ( 6854 hom. )

Consequence

PITPNM3
NM_031220.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 3.82

Variant links:

Genes affected

PITPNM3 (HGNC:21043): (PITPNM family member 3) This gene encodes a member of a family of membrane-associated phosphatidylinositol transfer domain-containing proteins. The calcium-binding protein has phosphatidylinositol (PI) transfer activity and interacts with the protein tyrosine kinase PTK2B (also known as PYK2). The protein is homologous to a Drosophila protein that is implicated in the visual transduction pathway in flies. Mutations in this gene result in autosomal dominant cone dystrophy. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

PITPNM3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017623901).

BP6

Variant 17-6538056-G-A is Benign according to our data. Variant chr17-6538056-G-A is described in ClinVar as [Benign]. Clinvar id is 261949.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PITPNM3	NM_031220.4 linkuse as main transcript	c.49C>T	p.Pro17Ser	missense_variant	2/20	ENST00000262483.13	NP_112497.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PITPNM3	ENST00000262483.13 linkuse as main transcript	c.49C>T	p.Pro17Ser	missense_variant	2/20	1	NM_031220.4	ENSP00000262483	P1	Q9BZ71-1
PITPNM3	ENST00000421306.7 linkuse as main transcript	c.49C>T	p.Pro17Ser	missense_variant	2/19	2		ENSP00000407882		Q9BZ71-3

Frequencies

GnomAD3 genomes

AF:

0.0820

AC:

12461

AN:

152054

Hom.:

598

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0433

Gnomad AMI

AF:

0.102

Gnomad AMR

AF:

0.0823

Gnomad ASJ

AF:

0.192

Gnomad EAS

AF:

0.00678

Gnomad SAS

AF:

0.0636

Gnomad FIN

AF:

0.107

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.102

Gnomad OTH

AF:

0.0847

GnomAD3 exomes

AF:

0.0836

AC:

20927

AN:

250446

Hom.:

1070

AF XY:

0.0859

AC XY:

11635

AN XY:

135510

show subpopulations

Gnomad AFR exome

AF:

0.0391

Gnomad AMR exome

AF:

0.0599

Gnomad ASJ exome

AF:

0.179

Gnomad EAS exome

AF:

0.0109

Gnomad SAS exome

AF:

0.0623

Gnomad FIN exome

AF:

0.107

Gnomad NFE exome

AF:

0.101

Gnomad OTH exome

AF:

0.0970

GnomAD4 exome

AF:

0.0929

AC:

135653

AN:

1460398

Hom.:

6854

Cov.:

AF XY:

0.0926

AC XY:

67296

AN XY:

726588

show subpopulations

Gnomad4 AFR exome

AF:

0.0426

Gnomad4 AMR exome

AF:

0.0610

Gnomad4 ASJ exome

AF:

0.173

Gnomad4 EAS exome

AF:

0.00499

Gnomad4 SAS exome

AF:

0.0639

Gnomad4 FIN exome

AF:

0.103

Gnomad4 NFE exome

AF:

0.0982

Gnomad4 OTH exome

AF:

0.0988

GnomAD4 genome

AF:

0.0819

AC:

12470

AN:

152172

Hom.:

598

Cov.:

AF XY:

0.0823

AC XY:

6125

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0435

Gnomad4 AMR

AF:

0.0822

Gnomad4 ASJ

AF:

0.192

Gnomad4 EAS

AF:

0.00680

Gnomad4 SAS

AF:

0.0638

Gnomad4 FIN

AF:

0.107

Gnomad4 NFE

AF:

0.102

Gnomad4 OTH

AF:

0.0838

Alfa

AF:

0.0984

Hom.:

1408

Bravo

AF:

0.0776

TwinsUK

AF:

0.102

AC:

379

ALSPAC

AF:

0.0926

AC:

357

ESP6500AA

AF:

0.0445

AC:

196

ESP6500EA

AF:

0.109

AC:

939

ExAC

AF:

0.0824

AC:

9998

Asia WGS

AF:

0.0430

AC:

150

AN:

3478

EpiCase

AF:

0.110

EpiControl

AF:

0.114

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 16, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Cone-rod dystrophy 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.014

.;T

Eigen

Benign

0.15

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.77

T;T

MetaRNN

Benign

0.0018

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

N;N

MutationTaster

Benign

0.87

P;P

PrimateAI

Uncertain

0.60

PROVEAN

Benign

1.3

N;N

REVEL

Benign

0.10

Sift

Benign

0.28

T;T

Sift4G

Benign

0.12

T;T

Polyphen

0.68

.;P

Vest4

0.33

MPC

1.0

ClinPred

0.020

GERP RS

4.9

Varity_R

0.097

gMVP

0.073

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