12-123142435-C-T

Variant names:

• chr12-123142435-C-T
• rs1106240
• NM_020845.3:c.-200+8318G>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.-200+8318G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.834 in 152,248 control chromosomes in the GnomAD database, including 53,241 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 0.83 (53241 hom., cov: 33)
• Consequence: PITPNM2 NM_020845.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77
• Publications: 32 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.95 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.-200+8318G>A		intron	N/A	NP_065896.1	Q9BZ72-1
	PITPNM2	NM_001300801.2		c.-200+8318G>A		intron	N/A	NP_001287730.1	Q9BZ72-2
	PITPNM2	NM_001384668.1		c.-200+8282G>A		intron	N/A	NP_001371597.1	Q9BZ72-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PITPNM2	ENST00000320201.10	TSL:5 MANE Select	c.-200+8318G>A		intron	N/A	ENSP00000322218.4	Q9BZ72-1
	PITPNM2	ENST00000931311.1		c.-200+8318G>A		intron	N/A	ENSP00000601370.1
	PITPNM2	ENST00000876868.1		c.-200+8318G>A		intron	N/A	ENSP00000546927.1

Frequencies

GnomAD3 genomes AF: 0.834 AC: 126842 AN: 152130 Hom.: 53185 Cov.: 33

Gnomad AFR AF: 0.910

Gnomad AMI AF: 0.830

Gnomad AMR AF: 0.821

Gnomad ASJ AF: 0.736

Gnomad EAS AF: 0.972

Gnomad SAS AF: 0.741

Gnomad FIN AF: 0.803

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.797

Gnomad OTH AF: 0.824

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

GnomAD4 genome AF: 0.834 AC: 126950 AN: 152248 Hom.: 53241 Cov.: 33 AF XY: 0.833 AC XY: 61979 AN XY: 74426

African (AFR) AF: 0.910 AC: 37811 AN: 41544

American (AMR) AF: 0.820 AC: 12540 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.736 AC: 2554 AN: 3468

East Asian (EAS) AF: 0.972 AC: 5036 AN: 5180

South Asian (SAS) AF: 0.741 AC: 3575 AN: 4826

European-Finnish (FIN) AF: 0.803 AC: 8498 AN: 10584

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.797 AC: 54222 AN: 68030

Other (OTH) AF: 0.826 AC: 1748 AN: 2116

Alfa AF: 0.803 Hom.: 84129

Bravo AF: 0.839

Asia WGS AF: 0.871 AC: 3027 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.0080
DANN	Benign	0.70
PhyloP100		-1.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1106240; hg19: chr12-123626982;