12-123017497-C-T

Variant names:

• chr12-123017497-C-T
• rs12425009
• NM_020845.3:c.79-3455G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020845.3(PITPNM2):​c.79-3455G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 152,114 control chromosomes in the GnomAD database, including 26,979 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 (26979 hom., cov: 33)
• Consequence: PITPNM2 NM_020845.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.174
• Publications: 11 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.702 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PITPNM2	NM_020845.3	MANE Select	c.79-3455G>A		intron	N/A	NP_065896.1	Q9BZ72-1
	PITPNM2	NM_001384660.1		c.79-3455G>A		intron	N/A	NP_001371589.1
	PITPNM2	NM_001300801.2		c.79-3455G>A		intron	N/A	NP_001287730.1	Q9BZ72-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PITPNM2	ENST00000320201.10	TSL:5 MANE Select	c.79-3455G>A		intron	N/A	ENSP00000322218.4	Q9BZ72-1
	PITPNM2	ENST00000451868.2	TSL:1	n.319-3455G>A		intron	N/A
	PITPNM2	ENST00000876870.1		c.79-3455G>A		intron	N/A	ENSP00000546929.1

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82674 AN: 151996 Hom.: 26986 Cov.: 33

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.719

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.582

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.543 AC: 82664 AN: 152114 Hom.: 26979 Cov.: 33 AF XY: 0.547 AC XY: 40694 AN XY: 74362

African (AFR) AF: 0.161 AC: 6668 AN: 41478

American (AMR) AF: 0.639 AC: 9767 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.619 AC: 2149 AN: 3470

East Asian (EAS) AF: 0.675 AC: 3492 AN: 5174

South Asian (SAS) AF: 0.578 AC: 2791 AN: 4828

European-Finnish (FIN) AF: 0.719 AC: 7598 AN: 10574

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.708 AC: 48123 AN: 67990

Other (OTH) AF: 0.580 AC: 1226 AN: 2114

Alfa AF: 0.618 Hom.: 45201

Bravo AF: 0.517

Asia WGS AF: 0.564 AC: 1961 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	14
DANN	Benign	0.38
PhyloP100		0.17
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12425009; hg19: chr12-123502044;