Genetic Variant NM_020845.3:c.-199-128C>T (chr12-123110616-G-A) – 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.-199-128C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 152,042 control chromosomes in the GnomAD database, including 26,840 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 0.54 ( 26840 hom., cov: 31)

Exomes 𝑓: 0.68 ( 28 hom. )

Failed GnomAD Quality Control

Consequence

PITPNM2
NM_020845.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.434

Publications

26 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:

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=-0.88).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PITPNM2	NM_020845.3 link	c.-199-128C>T		intron_variant	Intron 1 of 25	ENST00000320201.10	NP_065896.1	Q9BZ72-1Q9UF51

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PITPNM2	ENST00000320201.10 link	c.-199-128C>T	intron_variant	Intron 1 of 25	5	NM_020845.3	ENSP00000322218.4	Q9BZ72-1
PITPNM2	ENST00000542210.1 link	c.-199-128C>T	intron_variant	Intron 1 of 3	4		ENSP00000437869.1	F5H664
PITPNM2	ENST00000280562.9 link	c.-327C>T	upstream_gene_variant		5		ENSP00000280562.5	Q9BZ72-2
PITPNM2	ENST00000535289.1 link	n.-127C>T	upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.543

AC:

82458

AN:

151924

Hom.:

26848

Cov.:

show subpopulations

Gnomad AFR

AF:

0.161

Gnomad AMI

AF:

0.743

Gnomad AMR

AF:

0.638

Gnomad ASJ

AF:

0.616

Gnomad EAS

AF:

0.673

Gnomad SAS

AF:

0.596

Gnomad FIN

AF:

0.717

Gnomad MID

AF:

0.566

Gnomad NFE

AF:

0.705

Gnomad OTH

AF:

0.582

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.678

AC:

AN:

118

Hom.:

AF XY:

0.702

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.663

AC:

AN:

Other (OTH)

AF:

0.750

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.542

AC:

82449

AN:

152042

Hom.:

26840

Cov.:

AF XY:

0.546

AC XY:

40600

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.160

AC:

6654

AN:

41488

American (AMR)

AF:

0.638

AC:

9732

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.616

AC:

2137

AN:

3468

East Asian (EAS)

AF:

0.673

AC:

3480

AN:

5174

South Asian (SAS)

AF:

0.597

AC:

2875

AN:

4816

European-Finnish (FIN)

AF:

0.717

AC:

7576

AN:

10564

Middle Eastern (MID)

AF:

0.571

AC:

168

AN:

294

European-Non Finnish (NFE)

AF:

0.705

AC:

47924

AN:

67952

Other (OTH)

AF:

0.580

AC:

1227

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1491

2982

4473

5964

7455

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

688

1376

2064

2752

3440

<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:

0.648

Hom.:

15267

Bravo

AF:

0.515

Asia WGS

AF:

0.568

AC:

1975

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

6.7

(source)

DANN

Benign

0.49

PhyloP100

0.43

PromoterAI

0.022

Neutral

(source)

Splicing

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over