17-6483627-G-A

Position:

chr17-6483627-G-A

Variant summary

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

The NM_031220.4(PITPNM3):c.477C>T(p.Ser159Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0327 in 1,614,062 control chromosomes in the GnomAD database, including 1,644 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 142 hom., cov: 31)

Exomes 𝑓: 0.033 ( 1502 hom. )

Consequence

PITPNM3
NM_031220.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.51

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 17-6483627-G-A is Benign according to our data. Variant chr17-6483627-G-A is described in ClinVar as [Benign]. Clinvar id is 261948.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-6483627-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-4.51 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.123 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.477C>T	p.Ser159Ser	synonymous_variant	6/20	ENST00000262483.13	NP_112497.2	Q9BZ71-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PITPNM3	ENST00000262483.13 linkuse as main transcript	c.477C>T	p.Ser159Ser	synonymous_variant	6/20	1	NM_031220.4	ENSP00000262483.8		Q9BZ71-1
PITPNM3	ENST00000421306.7 linkuse as main transcript	c.369C>T	p.Ser123Ser	synonymous_variant	5/19	2		ENSP00000407882.3		Q9BZ71-3

Frequencies

GnomAD3 genomes

AF:

0.0301

AC:

4583

AN:

152058

Hom.:

140

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00891

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0780

Gnomad ASJ

AF:

0.0389

Gnomad EAS

AF:

0.0623

Gnomad SAS

AF:

0.131

Gnomad FIN

AF:

0.0240

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0231

Gnomad OTH

AF:

0.0413

GnomAD3 exomes

AF:

0.0499

AC:

12539

AN:

251264

Hom.:

594

AF XY:

0.0519

AC XY:

7056

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.00837

Gnomad AMR exome

AF:

0.107

Gnomad ASJ exome

AF:

0.0390

Gnomad EAS exome

AF:

0.0669

Gnomad SAS exome

AF:

0.121

Gnomad FIN exome

AF:

0.0238

Gnomad NFE exome

AF:

0.0227

Gnomad OTH exome

AF:

0.0491

GnomAD4 exome

AF:

0.0330

AC:

48215

AN:

1461886

Hom.:

1502

Cov.:

AF XY:

0.0354

AC XY:

25745

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00863

Gnomad4 AMR exome

AF:

0.105

Gnomad4 ASJ exome

AF:

0.0388

Gnomad4 EAS exome

AF:

0.0562

Gnomad4 SAS exome

AF:

0.118

Gnomad4 FIN exome

AF:

0.0228

Gnomad4 NFE exome

AF:

0.0231

Gnomad4 OTH exome

AF:

0.0406

GnomAD4 genome

AF:

0.0301

AC:

4586

AN:

152176

Hom.:

142

Cov.:

AF XY:

0.0325

AC XY:

2415

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.00888

Gnomad4 AMR

AF:

0.0781

Gnomad4 ASJ

AF:

0.0389

Gnomad4 EAS

AF:

0.0614

Gnomad4 SAS

AF:

0.131

Gnomad4 FIN

AF:

0.0240

Gnomad4 NFE

AF:

0.0231

Gnomad4 OTH

AF:

0.0437

Alfa

AF:

0.0180

Hom.:

Bravo

AF:

0.0330

Asia WGS

AF:

0.110

AC:

382

AN:

3478

EpiCase

AF:

0.0244

EpiControl

AF:

0.0260

ClinVar

Significance: Benign

Submissions summary: Benign:5

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 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 16, 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. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Cone-rod dystrophy 5

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.98

DANN

Benign

0.70

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