rs3809835

Positions:

chr17-6503563-C-T

Variant summary

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

The ENST00000262483.13(PITPNM3):c.238G>A(p.Ala80Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 1,609,844 control chromosomes in the GnomAD database, including 78,974 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A80V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.30 ( 7128 hom., cov: 32)

Exomes 𝑓: 0.31 ( 71846 hom. )

Consequence

PITPNM3
ENST00000262483.13 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.07

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=0.008624226).

BP6

Variant 17-6503563-C-T is Benign according to our data. Variant chr17-6503563-C-T is described in ClinVar as [Benign]. Clinvar id is 261945.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-6503563-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.329 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.238G>A	p.Ala80Thr	missense_variant	4/20	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.238G>A	p.Ala80Thr	missense_variant	4/20	1	NM_031220.4	ENSP00000262483	P1	Q9BZ71-1
PITPNM3	ENST00000421306.7 linkuse as main transcript	c.130G>A	p.Ala44Thr	missense_variant	3/19	2		ENSP00000407882		Q9BZ71-3

Frequencies

GnomAD3 genomes

AF:

0.305

AC:

46298

AN:

151932

Hom.:

7123

Cov.:

show subpopulations

Gnomad AFR

AF:

0.282

Gnomad AMI

AF:

0.340

Gnomad AMR

AF:

0.263

Gnomad ASJ

AF:

0.364

Gnomad EAS

AF:

0.256

Gnomad SAS

AF:

0.226

Gnomad FIN

AF:

0.306

Gnomad MID

AF:

0.453

Gnomad NFE

AF:

0.332

Gnomad OTH

AF:

0.323

GnomAD3 exomes

AF:

0.283

AC:

69696

AN:

246648

Hom.:

10440

AF XY:

0.287

AC XY:

38336

AN XY:

133566

show subpopulations

Gnomad AFR exome

AF:

0.285

Gnomad AMR exome

AF:

0.172

Gnomad ASJ exome

AF:

0.364

Gnomad EAS exome

AF:

0.257

Gnomad SAS exome

AF:

0.231

Gnomad FIN exome

AF:

0.303

Gnomad NFE exome

AF:

0.323

Gnomad OTH exome

AF:

0.301

GnomAD4 exome

AF:

0.310

AC:

452517

AN:

1457794

Hom.:

71846

Cov.:

AF XY:

0.309

AC XY:

224231

AN XY:

725242

show subpopulations

Gnomad4 AFR exome

AF:

0.287

Gnomad4 AMR exome

AF:

0.180

Gnomad4 ASJ exome

AF:

0.361

Gnomad4 EAS exome

AF:

0.244

Gnomad4 SAS exome

AF:

0.230

Gnomad4 FIN exome

AF:

0.298

Gnomad4 NFE exome

AF:

0.324

Gnomad4 OTH exome

AF:

0.316

GnomAD4 genome

AF:

0.305

AC:

46324

AN:

152050

Hom.:

7128

Cov.:

AF XY:

0.301

AC XY:

22376

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.283

Gnomad4 AMR

AF:

0.263

Gnomad4 ASJ

AF:

0.364

Gnomad4 EAS

AF:

0.257

Gnomad4 SAS

AF:

0.225

Gnomad4 FIN

AF:

0.306

Gnomad4 NFE

AF:

0.332

Gnomad4 OTH

AF:

0.319

Alfa

AF:

0.327

Hom.:

16967

Bravo

AF:

0.298

TwinsUK

AF:

0.334

AC:

1237

ALSPAC

AF:

0.325

AC:

1251

ESP6500AA

AF:

0.278

AC:

1224

ESP6500EA

AF:

0.336

AC:

2890

ExAC

AF:

0.283

AC:

34417

Asia WGS

AF:

0.215

AC:

751

AN:

3476

EpiCase

AF:

0.352

EpiControl

AF:

0.352

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 26, 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Cone-rod dystrophy 5

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.24

DANN

Benign

0.87

DEOGEN2

Benign

0.013

.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0096

LIST_S2

Benign

0.61

T;T

MetaRNN

Benign

0.0086

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.11

.;N

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.28

PROVEAN

Benign

0.63

N;N

REVEL

Benign

0.0090

Sift

Benign

0.78

T;T

Sift4G

Benign

0.62

T;T

Polyphen

0.0020

.;B

Vest4

0.058

MPC

0.45

ClinPred

0.0019

GERP RS

-1.6

Varity_R

0.022

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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