rs11654099

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_031220.4(PITPNM3):c.2430T>C(p.Asp810Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.856 in 1,614,072 control chromosomes in the GnomAD database, including 592,665 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.89 ( 60029 hom., cov: 35)

Exomes 𝑓: 0.85 ( 532636 hom. )

Consequence

PITPNM3
NM_031220.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.25

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 17-6461433-A-G is Benign according to our data. Variant chr17-6461433-A-G is described in ClinVar as [Benign]. Clinvar id is 261946.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-6461433-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.25 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.962 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.2430T>C	p.Asp810Asp	synonymous_variant	18/20	ENST00000262483.13	NP_112497.2	Q9BZ71-1
PITPNM3	NM_001165966.2 linkuse as main transcript	c.2322T>C	p.Asp774Asp	synonymous_variant	17/19		NP_001159438.1	A1A5C9
PITPNM3	XM_011524015.4 linkuse as main transcript	c.2430T>C	p.Asp810Asp	synonymous_variant	18/19		XP_011522317.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PITPNM3	ENST00000262483.13 linkuse as main transcript	c.2430T>C	p.Asp810Asp	synonymous_variant	18/20	1	NM_031220.4	ENSP00000262483.8		Q9BZ71-1

Frequencies

GnomAD3 genomes

AF:

0.885

AC:

134755

AN:

152186

Hom.:

59962

Cov.:

show subpopulations

Gnomad AFR

AF:

0.970

Gnomad AMI

AF:

0.936

Gnomad AMR

AF:

0.855

Gnomad ASJ

AF:

0.904

Gnomad EAS

AF:

0.910

Gnomad SAS

AF:

0.889

Gnomad FIN

AF:

0.816

Gnomad MID

AF:

0.962

Gnomad NFE

AF:

0.847

Gnomad OTH

AF:

0.887

GnomAD3 exomes

AF:

0.866

AC:

217761

AN:

251410

Hom.:

94582

AF XY:

0.866

AC XY:

117668

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.974

Gnomad AMR exome

AF:

0.856

Gnomad ASJ exome

AF:

0.906

Gnomad EAS exome

AF:

0.906

Gnomad SAS exome

AF:

0.883

Gnomad FIN exome

AF:

0.818

Gnomad NFE exome

AF:

0.848

Gnomad OTH exome

AF:

0.870

GnomAD4 exome

AF:

0.853

AC:

1246719

AN:

1461768

Hom.:

532636

Cov.:

AF XY:

0.854

AC XY:

620769

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.977

Gnomad4 AMR exome

AF:

0.852

Gnomad4 ASJ exome

AF:

0.903

Gnomad4 EAS exome

AF:

0.927

Gnomad4 SAS exome

AF:

0.880

Gnomad4 FIN exome

AF:

0.820

Gnomad4 NFE exome

AF:

0.844

Gnomad4 OTH exome

AF:

0.869

GnomAD4 genome

AF:

0.886

AC:

134882

AN:

152304

Hom.:

60029

Cov.:

AF XY:

0.885

AC XY:

65887

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.970

Gnomad4 AMR

AF:

0.855

Gnomad4 ASJ

AF:

0.904

Gnomad4 EAS

AF:

0.910

Gnomad4 SAS

AF:

0.889

Gnomad4 FIN

AF:

0.816

Gnomad4 NFE

AF:

0.847

Gnomad4 OTH

AF:

0.889

Alfa

AF:

0.862

Hom.:

66554

Bravo

AF:

0.894

Asia WGS

AF:

0.906

AC:

3151

AN:

3478

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	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	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Cone-rod dystrophy 5

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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. -

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

-0.81

CADD

Benign

0.22

DANN

Benign

0.51

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