12-123142435-C-T

Position:

• chr12-123142435-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PITPNM2	NM_020845.3	c.-200+8318G>A		intron_variant		ENST00000320201.10	NP_065896.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PITPNM2	ENST00000320201.10	c.-200+8318G>A		intron_variant		5	NM_020845.3	ENSP00000322218	P3
PITPNM2	ENST00000542210.1	c.-200+7341G>A		intron_variant		4		ENSP00000437869

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

Gnomad4 AFR AF: 0.910

Gnomad4 AMR AF: 0.820

Gnomad4 ASJ AF: 0.736

Gnomad4 EAS AF: 0.972

Gnomad4 SAS AF: 0.741

Gnomad4 FIN AF: 0.803

Gnomad4 NFE AF: 0.797

Gnomad4 OTH AF: 0.826

Alfa AF: 0.798 Hom.: 66068

Bravo AF: 0.839

Asia WGS AF: 0.871 AC: 3027 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1106240; hg19: chr12-123626982;