rs949143

Positions:

• chr12-123110616-G-A
• chr12-123110616-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.434

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=-0.88).
• 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/exons	MANE	Protein	UniProt
PITPNM2	NM_020845.3	c.-199-128C>T		intron_variant		ENST00000320201.10	NP_065896.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PITPNM2	ENST00000320201.10	c.-199-128C>T		intron_variant		5	NM_020845.3	ENSP00000322218.4
PITPNM2	ENST00000542210.1	c.-199-128C>T		intron_variant		4		ENSP00000437869.1

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82458 AN: 151924 Hom.: 26848 Cov.: 31

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: 80 AN: 118 Hom.: 28 AF XY: 0.702 AC XY: 59 AN XY: 84

Gnomad4 AFR exome AF: 0.250

Gnomad4 ASJ exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.663

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.542 AC: 82449 AN: 152042 Hom.: 26840 Cov.: 31 AF XY: 0.546 AC XY: 40600 AN XY: 74316

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.638

Gnomad4 ASJ AF: 0.616

Gnomad4 EAS AF: 0.673

Gnomad4 SAS AF: 0.597

Gnomad4 FIN AF: 0.717

Gnomad4 NFE AF: 0.705

Gnomad4 OTH AF: 0.580

Alfa AF: 0.643 Hom.: 13426

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
DANN	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs949143; hg19: chr12-123595163;