dbSNP rs938288: PITPNM3:p.Thr235Thr (chr17-6478619-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -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

Clinical Significance

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

Conservation

PhyloP100: -2.38

Publications

22 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 -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031220.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PITPNM3	NM_031220.4	MANE Select	c.705C>T	p.Thr235Thr	synonymous	Exon 7 of 20	NP_112497.2	Q9BZ71-1
	PITPNM3	NM_001165966.2		c.597C>T	p.Thr199Thr	synonymous	Exon 6 of 19	NP_001159438.1	Q9BZ71-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PITPNM3	ENST00000262483.13	TSL:1 MANE Select	c.705C>T	p.Thr235Thr	synonymous	Exon 7 of 20	ENSP00000262483.8	Q9BZ71-1
PITPNM3	ENST00000572795.1	TSL:1	n.3211C>T		non_coding_transcript_exon	Exon 1 of 14
PITPNM3	ENST00000421306.7	TSL:2	c.597C>T	p.Thr199Thr	synonymous	Exon 6 of 19	ENSP00000407882.3	Q9BZ71-3

Frequencies

GnomAD3 genomes

AF:

0.505

AC:

76724

AN:

151920

Hom.:

21194

Cov.:

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

GnomAD2 exomes

AF:

0.530

AC:

132573

AN:

250108

AF XY:

0.536

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 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.:

AF XY:

0.587

AC XY:

426430

AN XY:

726978

show subpopulations

African (AFR)

AF:

0.280

AC:

9389

AN:

33480

American (AMR)

AF:

0.500

AC:

22334

AN:

44654

Ashkenazi Jewish (ASJ)

AF:

0.613

AC:

16014

AN:

26132

East Asian (EAS)

AF:

0.230

AC:

9149

AN:

39694

South Asian (SAS)

AF:

0.436

AC:

37635

AN:

86226

European-Finnish (FIN)

AF:

0.605

AC:

32244

AN:

53326

Middle Eastern (MID)

AF:

0.625

AC:

3603

AN:

5766

European-Non Finnish (NFE)

AF:

0.626

AC:

695999

AN:

1111756

Other (OTH)

AF:

0.569

AC:

34375

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

21510

43020

64530

86040

107550

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18254

36508

54762

73016

91270

<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:

0.505

AC:

76730

AN:

152038

Hom.:

21195

Cov.:

AF XY:

0.503

AC XY:

37357

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.295

AC:

12230

AN:

41460

American (AMR)

AF:

0.533

AC:

8147

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.601

AC:

2084

AN:

3470

East Asian (EAS)

AF:

0.243

AC:

1255

AN:

5162

South Asian (SAS)

AF:

0.408

AC:

1965

AN:

4818

European-Finnish (FIN)

AF:

0.619

AC:

6544

AN:

10570

Middle Eastern (MID)

AF:

0.643

AC:

189

AN:

294

European-Non Finnish (NFE)

AF:

0.628

AC:

42661

AN:

67956

Other (OTH)

AF:

0.551

AC:

1163

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1825

3650

5475

7300

9125

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

666

1332

1998

2664

3330

<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:

0.579

Hom.:

72983

Bravo

AF:

0.490

Asia WGS

AF:

0.340

AC:

1187

AN:

3478

EpiCase

AF:

0.644

EpiControl

AF:

0.641

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Cone-rod dystrophy 5 (2)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.069

(source)

DANN

Benign

0.78

PhyloP100

-2.4

Mutation Taster

=100/0

polymorphism (auto)

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over