Genetic Variant NM_031220.4:c.*3555delA (chr17-6451782-GT-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_031220.4(PITPNM3):c.*3555delA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.90 ( 60964 hom., cov: 0)

Exomes 𝑓: 0.83 ( 8 hom. )

Consequence

PITPNM3
NM_031220.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.604

Publications

2 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 -10 ACMG points.

BP6

Variant 17-6451782-GT-G is Benign according to our data. Variant chr17-6451782-GT-G is described in ClinVar as Benign. ClinVar VariationId is 324659.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.941 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.*3555delA		3_prime_UTR	Exon 20 of 20	NP_112497.2	Q9BZ71-1
	PITPNM3	NM_001165966.2		c.*3555delA		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.*3555delA		3_prime_UTR	Exon 20 of 20	ENSP00000262483.8	Q9BZ71-1
	PITPNM3	ENST00000421306.7	TSL:2	c.*3555delA		3_prime_UTR	Exon 19 of 19	ENSP00000407882.3	Q9BZ71-3

Frequencies

GnomAD3 genomes

AF:

0.895

AC:

135661

AN:

151506

Hom.:

60917

Cov.:

show subpopulations

Gnomad AFR

AF:

0.948

Gnomad AMI

AF:

0.897

Gnomad AMR

AF:

0.877

Gnomad ASJ

AF:

0.876

Gnomad EAS

AF:

0.853

Gnomad SAS

AF:

0.857

Gnomad FIN

AF:

0.859

Gnomad MID

AF:

0.908

Gnomad NFE

AF:

0.880

Gnomad OTH

AF:

0.890

GnomAD4 exome

AF:

0.833

AC:

AN:

Hom.:

Cov.:

AF XY:

0.850

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.850

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.588

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.895

AC:

135765

AN:

151622

Hom.:

60964

Cov.:

AF XY:

0.895

AC XY:

66264

AN XY:

74044

show subpopulations

African (AFR)

AF:

0.948

AC:

39162

AN:

41290

American (AMR)

AF:

0.877

AC:

13363

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.876

AC:

3039

AN:

3468

East Asian (EAS)

AF:

0.853

AC:

4360

AN:

5114

South Asian (SAS)

AF:

0.856

AC:

4113

AN:

4804

European-Finnish (FIN)

AF:

0.859

AC:

9007

AN:

10482

Middle Eastern (MID)

AF:

0.911

AC:

266

AN:

292

European-Non Finnish (NFE)

AF:

0.880

AC:

59761

AN:

67918

Other (OTH)

AF:

0.890

AC:

1878

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

679

1358

2038

2717

3396

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

898

1796

2694

3592

4490

<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:

0.890

Hom.:

6462

Bravo

AF:

0.893

Asia WGS

AF:

0.848

AC:

2949

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cone-Rod Dystrophy, Dominant (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.60

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

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