chr17-6470417-C-T

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.1625-9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 1,613,536 control chromosomes in the GnomAD database, including 148,767 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 11240 hom., cov: 33)

Exomes 𝑓: 0.43 ( 137527 hom. )

Consequence

PITPNM3
NM_031220.4 intron

Scores

Splicing: ADA: 0.00009036

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.428

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=-0.83).

BP6

Variant 17-6470417-C-T is Benign according to our data. Variant chr17-6470417-C-T is described in ClinVar as [Benign]. Clinvar id is 194273.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PITPNM3	NM_031220.4 link	c.1625-9G>A		intron_variant	Intron 12 of 19	ENST00000262483.13	NP_112497.2	Q9BZ71-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PITPNM3	ENST00000262483.13 link	c.1625-9G>A	intron_variant	Intron 12 of 19	1	NM_031220.4	ENSP00000262483.8	Q9BZ71-1
PITPNM3	ENST00000572795.1 link	n.4131-9G>A	intron_variant	Intron 6 of 13	1
PITPNM3	ENST00000576664.5 link	n.374-9G>A	intron_variant	Intron 3 of 10	1
PITPNM3	ENST00000421306.7 link	c.1517-9G>A	intron_variant	Intron 11 of 18	2		ENSP00000407882.3	Q9BZ71-3

Frequencies

GnomAD3 genomes

AF:

0.366

AC:

55545

AN:

151942

Hom.:

11240

Cov.:

show subpopulations

Gnomad AFR

AF:

0.205

Gnomad AMI

AF:

0.485

Gnomad AMR

AF:

0.377

Gnomad ASJ

AF:

0.459

Gnomad EAS

AF:

0.188

Gnomad SAS

AF:

0.229

Gnomad FIN

AF:

0.438

Gnomad MID

AF:

0.563

Gnomad NFE

AF:

0.464

Gnomad OTH

AF:

0.416

GnomAD3 exomes

AF:

0.377

AC:

94198

AN:

249992

Hom.:

19252

AF XY:

0.380

AC XY:

51393

AN XY:

135412

show subpopulations

Gnomad AFR exome

AF:

0.197

Gnomad AMR exome

AF:

0.338

Gnomad ASJ exome

AF:

0.470

Gnomad EAS exome

AF:

0.193

Gnomad SAS exome

AF:

0.247

Gnomad FIN exome

AF:

0.424

Gnomad NFE exome

AF:

0.460

Gnomad OTH exome

AF:

0.425

GnomAD4 exome

AF:

0.426

AC:

623070

AN:

1461476

Hom.:

137527

Cov.:

AF XY:

0.423

AC XY:

307435

AN XY:

727016

show subpopulations

Gnomad4 AFR exome

AF:

0.195

Gnomad4 AMR exome

AF:

0.340

Gnomad4 ASJ exome

AF:

0.467

Gnomad4 EAS exome

AF:

0.184

Gnomad4 SAS exome

AF:

0.251

Gnomad4 FIN exome

AF:

0.421

Gnomad4 NFE exome

AF:

0.459

Gnomad4 OTH exome

AF:

0.417

GnomAD4 genome

AF:

0.365

AC:

55548

AN:

152060

Hom.:

11240

Cov.:

AF XY:

0.362

AC XY:

26940

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.205

Gnomad4 AMR

AF:

0.377

Gnomad4 ASJ

AF:

0.459

Gnomad4 EAS

AF:

0.188

Gnomad4 SAS

AF:

0.229

Gnomad4 FIN

AF:

0.438

Gnomad4 NFE

AF:

0.464

Gnomad4 OTH

AF:

0.412

Alfa

AF:

0.424

Hom.:

5927

Bravo

AF:

0.358

Asia WGS

AF:

0.220

AC:

771

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:2

Oct 27, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cone-rod dystrophy 5

Benign:2

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

-0.83

CADD

Benign

4.0

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000090

dbscSNV1_RF

Benign

0.0020

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