dbSNP rs373992381: PITPNM3:c.2620-19C>T (chr17-6455662-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_031220.4(PITPNM3):c.2620-19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000814 in 1,474,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000025 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0000077 ( 0 hom. )

Consequence

PITPNM3
NM_031220.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.164

Publications

0 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.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BS2

High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PITPNM3	NM_031220.4 link	c.2620-19C>T		intron_variant	Intron 19 of 19	ENST00000262483.13	NP_112497.2	Q9BZ71-1
PITPNM3	NM_001165966.2 link	c.2512-19C>T		intron_variant	Intron 18 of 18		NP_001159438.1	A1A5C9

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PITPNM3	ENST00000262483.13 link	c.2620-19C>T	intron_variant	Intron 19 of 19	1	NM_031220.4	ENSP00000262483.8	Q9BZ71-1
PITPNM3	ENST00000572795.1 link	n.5126-19C>T	intron_variant	Intron 13 of 13	1
PITPNM3	ENST00000576664.5 link	n.1369-19C>T	intron_variant	Intron 10 of 10	1
PITPNM3	ENST00000421306.7 link	c.2512-19C>T	intron_variant	Intron 18 of 18	2		ENSP00000407882.3	Q9BZ71-3

Frequencies

GnomAD3 genomes

AF:

0.0000248

AC:

AN:

40292

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000547

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000927

AC:

AN:

215720

AF XY:

0.0000166

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000202

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000767

AC:

AN:

1433758

Hom.:

Cov.:

AF XY:

0.00000701

AC XY:

AN XY:

713728

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33042

American (AMR)

AF:

0.00

AC:

AN:

44198

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25800

East Asian (EAS)

AF:

0.00

AC:

AN:

39302

South Asian (SAS)

AF:

0.00

AC:

AN:

85468

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37348

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5108

European-Non Finnish (NFE)

AF:

0.00000996

AC:

AN:

1103898

Other (OTH)

AF:

0.00

AC:

AN:

59594

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.539

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000248

AC:

AN:

40292

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

19718

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

10730

American (AMR)

AF:

0.00

AC:

AN:

3084

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

814

East Asian (EAS)

AF:

0.00

AC:

AN:

2416

South Asian (SAS)

AF:

0.00

AC:

AN:

1498

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2698

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0000547

AC:

AN:

18280

Other (OTH)

AF:

0.00

AC:

AN:

480

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.0

(source)

DANN

Benign

0.75

PhyloP100

0.16

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over