12-122985100-G-T

Position:

• chr12-122985100-G-T

Variant summary

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

The NM_020845.3(PITPNM2):​c.*927C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 152,482 control chromosomes in the GnomAD database, including 26,935 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 (26843 hom., cov: 33)
  • Exomes 𝑓: 0.74 (92 hom.)
• Consequence: PITPNM2 NM_020845.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.17

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=-0.57).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PITPNM2	NM_020845.3	c.*927C>A		3_prime_UTR_variant	26/26	ENST00000320201.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PITPNM2	ENST00000320201.10	c.*927C>A		3_prime_UTR_variant	26/26	5	NM_020845.3	P3
PITPNM2	ENST00000280562.9	c.*927C>A		3_prime_UTR_variant	25/25	5		A2

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82172 AN: 152020 Hom.: 26849 Cov.: 33

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.578

GnomAD4 exome AF: 0.735 AC: 253 AN: 344 Hom.: 92 Cov.: 0 AF XY: 0.735 AC XY: 144 AN XY: 196

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.744

Gnomad4 NFE exome AF: 0.625

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.540 AC: 82165 AN: 152138 Hom.: 26843 Cov.: 33 AF XY: 0.544 AC XY: 40456 AN XY: 74376

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.637

Gnomad4 ASJ AF: 0.619

Gnomad4 EAS AF: 0.673

Gnomad4 SAS AF: 0.577

Gnomad4 FIN AF: 0.718

Gnomad4 NFE AF: 0.707

Gnomad4 OTH AF: 0.576

Alfa AF: 0.500 Hom.: 1856

Bravo AF: 0.513

Asia WGS AF: 0.563 AC: 1958 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	14
DANN	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3741530; hg19: chr12-123469647;