rs149964592

Positions:

chr17-6478625-G-A

Variant summary

Our verdict is Benign. Variant got -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

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:

PITPNM3 (HGNC:):

PITPNM3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 261950.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-6478625-G-A is described in Lovd as [Likely_benign].

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/exons	MANE	Protein	UniProt
PITPNM3	NM_031220.4 linkuse as main transcript	c.699C>T	p.Val233Val	synonymous_variant	7/20	ENST00000262483.13	NP_112497.2	Q9BZ71-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PITPNM3	ENST00000262483.13 linkuse as main transcript	c.699C>T	p.Val233Val	synonymous_variant	7/20	1	NM_031220.4	ENSP00000262483.8	Q9BZ71-1
PITPNM3	ENST00000572795.1 linkuse as main transcript	n.3205C>T		non_coding_transcript_exon_variant	1/14	1
PITPNM3	ENST00000421306.7 linkuse as main transcript	c.591C>T	p.Val197Val	synonymous_variant	6/19	2		ENSP00000407882.3	Q9BZ71-3

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

GnomAD3 exomes

AF:

0.00778

AC:

1950

AN:

250582

Hom.:

AF XY:

0.00787

AC XY:

1067

AN XY:

135656

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 SAS exome

AF:

0.00219

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

Gnomad4 AFR exome

AF:

0.00140

Gnomad4 AMR exome

AF:

0.00875

Gnomad4 ASJ exome

AF:

0.0123

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00276

Gnomad4 FIN exome

AF:

0.00283

Gnomad4 NFE exome

AF:

0.0105

Gnomad4 OTH exome

AF:

0.00835

GnomAD4 genome

AF:

0.00691

AC:

1052

AN:

152268

Hom.:

Cov.:

AF XY:

0.00670

AC XY:

499

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00207

Gnomad4 AMR

AF:

0.0109

Gnomad4 ASJ

AF:

0.0124

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00103

Gnomad4 FIN

AF:

0.00283

Gnomad4 NFE

AF:

0.00983

Gnomad4 OTH

AF:

0.0147

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	PITPNM3: BP4, BP7, BS1, BS2 -

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. -
Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Sep 01, 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

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.16

DANN

Benign

0.75

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