Genetic Variant PITPNM3:c.*3453_*3454insA (chr17-6451884-C-CT) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_031220.4(PITPNM3):c.*3453_*3454insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.36 ( 7115 hom., cov: 0)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PITPNM3
NM_031220.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.00

Publications

1 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 -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.499 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.3453_3454insA		3_prime_UTR	Exon 20 of 20	NP_112497.2	Q9BZ71-1
	PITPNM3	NM_001165966.2		c.3453_3454insA		3_prime_UTR	Exon 19 of 19	NP_001159438.1	Q9BZ71-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PITPNM3	ENST00000262483.13	TSL:1 MANE Select	c.3453_3454insA		3_prime_UTR	Exon 20 of 20	ENSP00000262483.8	Q9BZ71-1
	PITPNM3	ENST00000421306.7	TSL:2	c.3453_3454insA		3_prime_UTR	Exon 19 of 19	ENSP00000407882.3	Q9BZ71-3

Frequencies

GnomAD3 genomes

AF:

0.355

AC:

27898

AN:

78486

Hom.:

7113

Cov.:

show subpopulations

Gnomad AFR

AF:

0.174

Gnomad AMI

AF:

0.407

Gnomad AMR

AF:

0.382

Gnomad ASJ

AF:

0.287

Gnomad EAS

AF:

0.518

Gnomad SAS

AF:

0.512

Gnomad FIN

AF:

0.441

Gnomad MID

AF:

0.197

Gnomad NFE

AF:

0.393

Gnomad OTH

AF:

0.335

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.355

AC:

27908

AN:

78540

Hom.:

7115

Cov.:

AF XY:

0.364

AC XY:

13933

AN XY:

38312

show subpopulations

African (AFR)

AF:

0.174

AC:

2928

AN:

16806

American (AMR)

AF:

0.382

AC:

2804

AN:

7336

Ashkenazi Jewish (ASJ)

AF:

0.287

AC:

552

AN:

1920

East Asian (EAS)

AF:

0.518

AC:

1929

AN:

3724

South Asian (SAS)

AF:

0.513

AC:

1455

AN:

2838

European-Finnish (FIN)

AF:

0.441

AC:

2554

AN:

5788

Middle Eastern (MID)

AF:

0.184

AC:

AN:

174

European-Non Finnish (NFE)

AF:

0.393

AC:

15122

AN:

38464

Other (OTH)

AF:

0.333

AC:

335

AN:

1006

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.594

Heterozygous variant carriers

451

902

1352

1803

2254

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

276

552

828

1104

1380

<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:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cone-Rod Dystrophy, Dominant (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.0

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over