rs149964592

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_031220.4(PITPNM3):c.699C>T(p.Val233Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00895 in 1,614,006 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0069 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0092 ( 85 hom. )

Consequence

PITPNM3
NM_031220.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.70

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

cone-rod dystrophy 5
Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
cone-rod dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

PITPNM3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 17-6478625-G-A is Benign according to our data. Variant chr17-6478625-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 261950.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.7 with no splicing effect.

BS2

High AC in GnomAd4 at 1052 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PITPNM3	NM_031220.4 link	c.699C>T	p.Val233Val	synonymous_variant	Exon 7 of 20	ENST00000262483.13	NP_112497.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
PITPNM3	ENST00000262483.13 link	c.699C>T	p.Val233Val	synonymous_variant	Exon 7 of 20	1	NM_031220.4	ENSP00000262483.8
PITPNM3	ENST00000572795.1 link	n.3205C>T		non_coding_transcript_exon_variant	Exon 1 of 14	1
PITPNM3	ENST00000421306.7 link	c.591C>T	p.Val197Val	synonymous_variant	Exon 6 of 19	2		ENSP00000407882.3

Frequencies

GnomAD3 genomes

AF:

0.00692

AC:

1053

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00208

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.0109

Gnomad ASJ

AF:

0.0124

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00283

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00983

Gnomad OTH

AF:

0.0148

GnomAD2 exomes

AF:

0.00778

AC:

1950

AN:

250582

AF XY:

0.00787

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.00848

Gnomad ASJ exome

AF:

0.0123

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00269

Gnomad NFE exome

AF:

0.0115

Gnomad OTH exome

AF:

0.0134

GnomAD4 exome

AF:

0.00916

AC:

13388

AN:

1461738

Hom.:

Cov.:

AF XY:

0.00900

AC XY:

6541

AN XY:

727160

show subpopulations

African (AFR)

AF:

0.00140

AC:

AN:

33480

American (AMR)

AF:

0.00875

AC:

391

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.0123

AC:

321

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00276

AC:

238

AN:

86240

European-Finnish (FIN)

AF:

0.00283

AC:

151

AN:

53370

Middle Eastern (MID)

AF:

0.0118

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0105

AC:

11668

AN:

1111954

Other (OTH)

AF:

0.00835

AC:

504

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

773

1545

2318

3090

3863

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

432

864

1296

1728

2160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00691

AC:

1052

AN:

152268

Hom.:

Cov.:

AF XY:

0.00670

AC XY:

499

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.00207

AC:

AN:

41548

American (AMR)

AF:

0.0109

AC:

166

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0124

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.00103

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00283

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00983

AC:

669

AN:

68030

Other (OTH)

AF:

0.0147

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

110

165

220

275

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00919

Hom.:

Bravo

AF:

0.00828

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0117

EpiControl

AF:

0.0132

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

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 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PITPNM3: BP4, BP7, BS1, BS2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Cone-rod dystrophy 5

Benign:2

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.

Sep 01, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.16

(source)

DANN

Benign

0.75

PhyloP100

-1.7

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over