rs73346359

Variant names:

Variant summary

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

The NM_031220.4(PITPNM3):c.2307-5A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0577 in 1,613,868 control chromosomes in the GnomAD database, including 3,574 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.083 ( 730 hom., cov: 33)

Exomes 𝑓: 0.055 ( 2844 hom. )

Consequence

PITPNM3
NM_031220.4 splice_region, intron

Scores

Splicing: ADA: 0.00003512

Clinical Significance

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

Conservation

PhyloP100: -1.21

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 (BayesDel_noAF=-0.94).

BP6

Variant 17-6461561-T-C is Benign according to our data. Variant chr17-6461561-T-C is described in ClinVar as [Benign]. Clinvar id is 261944.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PITPNM3	NM_031220.4 link	c.2307-5A>G	splice_region_variant, intron_variant	Intron 17 of 19	ENST00000262483.13	NP_112497.2	Q9BZ71-1
PITPNM3	NM_001165966.2 link	c.2199-5A>G	splice_region_variant, intron_variant	Intron 16 of 18		NP_001159438.1	A1A5C9
PITPNM3	XM_011524015.4 link	c.2307-5A>G	splice_region_variant, intron_variant	Intron 17 of 18		XP_011522317.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PITPNM3	ENST00000262483.13 link	c.2307-5A>G		splice_region_variant, intron_variant	Intron 17 of 19	1	NM_031220.4	ENSP00000262483.8		Q9BZ71-1

Frequencies

GnomAD3 genomes

AF:

0.0832

AC:

12653

AN:

152140

Hom.:

719

Cov.:

show subpopulations

Gnomad AFR

AF:

0.159

Gnomad AMI

AF:

0.0440

Gnomad AMR

AF:

0.0386

Gnomad ASJ

AF:

0.0170

Gnomad EAS

AF:

0.168

Gnomad SAS

AF:

0.0488

Gnomad FIN

AF:

0.0663

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0505

Gnomad OTH

AF:

0.0611

GnomAD3 exomes

AF:

0.0594

AC:

14933

AN:

251260

Hom.:

702

AF XY:

0.0575

AC XY:

7803

AN XY:

135800

show subpopulations

Gnomad AFR exome

AF:

0.158

Gnomad AMR exome

AF:

0.0228

Gnomad ASJ exome

AF:

0.0146

Gnomad EAS exome

AF:

0.162

Gnomad SAS exome

AF:

0.0469

Gnomad FIN exome

AF:

0.0657

Gnomad NFE exome

AF:

0.0467

Gnomad OTH exome

AF:

0.0458

GnomAD4 exome

AF:

0.0551

AC:

80495

AN:

1461610

Hom.:

2844

Cov.:

AF XY:

0.0543

AC XY:

39487

AN XY:

727116

show subpopulations

Gnomad4 AFR exome

AF:

0.164

Gnomad4 AMR exome

AF:

0.0239

Gnomad4 ASJ exome

AF:

0.0165

Gnomad4 EAS exome

AF:

0.156

Gnomad4 SAS exome

AF:

0.0451

Gnomad4 FIN exome

AF:

0.0643

Gnomad4 NFE exome

AF:

0.0507

Gnomad4 OTH exome

AF:

0.0575

GnomAD4 genome

AF:

0.0834

AC:

12705

AN:

152258

Hom.:

730

Cov.:

AF XY:

0.0833

AC XY:

6202

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.160

Gnomad4 AMR

AF:

0.0385

Gnomad4 ASJ

AF:

0.0170

Gnomad4 EAS

AF:

0.169

Gnomad4 SAS

AF:

0.0487

Gnomad4 FIN

AF:

0.0663

Gnomad4 NFE

AF:

0.0505

Gnomad4 OTH

AF:

0.0624

Alfa

AF:

0.0592

Hom.:

194

Bravo

AF:

0.0840

Asia WGS

AF:

0.124

AC:

430

AN:

3478

EpiCase

AF:

0.0435

EpiControl

AF:

0.0438

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 30, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cone-rod dystrophy 5

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.015

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000035

dbscSNV1_RF

Benign

0.012

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