rs938288

Variant summary

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

The NM_031220.4(PITPNM3):​c.705C>T​(p.Thr235Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 1,613,450 control chromosomes in the GnomAD database, including 281,443 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 21195 hom., cov: 32)
Exomes 𝑓: 0.59 ( 260248 hom. )

Consequence

PITPNM3
NM_031220.4 synonymous

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -2.38
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
Variant 17-6478619-G-A is Benign according to our data. Variant chr17-6478619-G-A is described in ClinVar as [Benign]. Clinvar id is 261951.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-2.38 with no splicing effect.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PITPNM3NM_031220.4 linkc.705C>T p.Thr235Thr synonymous_variant Exon 7 of 20 ENST00000262483.13 NP_112497.2 Q9BZ71-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PITPNM3ENST00000262483.13 linkc.705C>T p.Thr235Thr synonymous_variant Exon 7 of 20 1 NM_031220.4 ENSP00000262483.8 Q9BZ71-1
PITPNM3ENST00000572795.1 linkn.3211C>T non_coding_transcript_exon_variant Exon 1 of 14 1
PITPNM3ENST00000421306.7 linkc.597C>T p.Thr199Thr synonymous_variant Exon 6 of 19 2 ENSP00000407882.3 Q9BZ71-3

Frequencies

GnomAD3 genomes
AF:
0.505
AC:
76724
AN:
151920
Hom.:
21194
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.295
Gnomad AMI
AF:
0.542
Gnomad AMR
AF:
0.533
Gnomad ASJ
AF:
0.601
Gnomad EAS
AF:
0.243
Gnomad SAS
AF:
0.407
Gnomad FIN
AF:
0.619
Gnomad MID
AF:
0.636
Gnomad NFE
AF:
0.628
Gnomad OTH
AF:
0.556
GnomAD3 exomes
AF:
0.530
AC:
132573
AN:
250108
Hom.:
37202
AF XY:
0.536
AC XY:
72508
AN XY:
135396
show subpopulations
Gnomad AFR exome
AF:
0.280
Gnomad AMR exome
AF:
0.496
Gnomad ASJ exome
AF:
0.615
Gnomad EAS exome
AF:
0.254
Gnomad SAS exome
AF:
0.429
Gnomad FIN exome
AF:
0.610
Gnomad NFE exome
AF:
0.623
Gnomad OTH exome
AF:
0.577
GnomAD4 exome
AF:
0.589
AC:
860742
AN:
1461412
Hom.:
260248
Cov.:
67
AF XY:
0.587
AC XY:
426430
AN XY:
726978
show subpopulations
Gnomad4 AFR exome
AF:
0.280
Gnomad4 AMR exome
AF:
0.500
Gnomad4 ASJ exome
AF:
0.613
Gnomad4 EAS exome
AF:
0.230
Gnomad4 SAS exome
AF:
0.436
Gnomad4 FIN exome
AF:
0.605
Gnomad4 NFE exome
AF:
0.626
Gnomad4 OTH exome
AF:
0.569
GnomAD4 genome
AF:
0.505
AC:
76730
AN:
152038
Hom.:
21195
Cov.:
32
AF XY:
0.503
AC XY:
37357
AN XY:
74286
show subpopulations
Gnomad4 AFR
AF:
0.295
Gnomad4 AMR
AF:
0.533
Gnomad4 ASJ
AF:
0.601
Gnomad4 EAS
AF:
0.243
Gnomad4 SAS
AF:
0.408
Gnomad4 FIN
AF:
0.619
Gnomad4 NFE
AF:
0.628
Gnomad4 OTH
AF:
0.551
Alfa
AF:
0.605
Hom.:
42951
Bravo
AF:
0.490
Asia WGS
AF:
0.340
AC:
1187
AN:
3478
EpiCase
AF:
0.644
EpiControl
AF:
0.641

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

- -

Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

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. -

not specified Benign:2
May 24, 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
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 05, 2021
Genome-Nilou Lab
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
-0.76
CADD
Benign
0.069
DANN
Benign
0.78

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.

Other links and lift over

dbSNP: rs938288; hg19: chr17-6381939; COSMIC: COSV52595054; API