Genetic Variant NM_020845.3:c.-96+19190T>C (chr12-123091195-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020845.3(PITPNM2):c.-96+19190T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.692 in 152,184 control chromosomes in the GnomAD database, including 36,601 homozygotes. 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 0.69 ( 36599 hom., cov: 33)

Exomes 𝑓: 0.50 ( 2 hom. )

Consequence

PITPNM2
NM_020845.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.75

Publications

39 publications found

Variant links:

Genes affected

PITPNM2 (HGNC:21044): (phosphatidylinositol transfer protein membrane associated 2) PITPNM2 belongs to a family of membrane-associated phosphatidylinositol transfer domain-containing proteins that share homology with the Drosophila retinal degeneration B (rdgB) protein (Ocaka et al., 2005 [PubMed 15627748]).[supplied by OMIM, Mar 2008]

PITPNM2 links:

ENSG00000280381 (HGNC:):

ENSG00000280381 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020845.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PITPNM2	NM_020845.3	MANE Select	c.-96+19190T>C	intron	N/A	NP_065896.1
PITPNM2	NM_001384660.1		c.-96+14160T>C	intron	N/A	NP_001371589.1
PITPNM2	NM_001300801.2		c.-96+19190T>C	intron	N/A	NP_001287730.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PITPNM2	ENST00000320201.10	TSL:5 MANE Select	c.-96+19190T>C	intron	N/A	ENSP00000322218.4
PITPNM2	ENST00000451868.2	TSL:1	n.145+14160T>C	intron	N/A
ENSG00000280381	ENST00000624878.1	TSL:6	n.1627T>C	non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.692

AC:

105248

AN:

152052

Hom.:

36573

Cov.:

show subpopulations

Gnomad AFR

AF:

0.668

Gnomad AMI

AF:

0.747

Gnomad AMR

AF:

0.700

Gnomad ASJ

AF:

0.636

Gnomad EAS

AF:

0.678

Gnomad SAS

AF:

0.605

Gnomad FIN

AF:

0.717

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.711

Gnomad OTH

AF:

0.690

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

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

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)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.625

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000907115), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.692

AC:

105321

AN:

152170

Hom.:

36599

Cov.:

AF XY:

0.691

AC XY:

51418

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.668

AC:

27731

AN:

41510

American (AMR)

AF:

0.699

AC:

10692

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.636

AC:

2208

AN:

3472

East Asian (EAS)

AF:

0.678

AC:

3500

AN:

5162

South Asian (SAS)

AF:

0.606

AC:

2921

AN:

4822

European-Finnish (FIN)

AF:

0.717

AC:

7602

AN:

10598

Middle Eastern (MID)

AF:

0.613

AC:

179

AN:

292

European-Non Finnish (NFE)

AF:

0.711

AC:

48357

AN:

67994

Other (OTH)

AF:

0.687

AC:

1450

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

1730

3459

5189

6918

8648

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

828

1656

2484

3312

4140

<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:

0.697

Hom.:

111008

Bravo

AF:

0.687

Asia WGS

AF:

0.618

AC:

2150

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.051

(source)

DANN

Benign

0.44

PhyloP100

-2.8

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