12-123091195-A-G

Variant names:

• chr12-123091195-A-G
• rs1727307
• NM_020845.3:c.-96+19190T>C

Variant summary

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

The NM_020845.3(PITPNM2):​c.-96+19190T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.692 in 152,184 control chromosomes in the GnomAD database, including 36,601 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 0.69 (36599 hom., cov: 33)
  • Exomes 𝑓: 0.50 (2 hom.)
• Consequence: PITPNM2 NM_020845.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.75
• Publications: 39 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]

ENSG00000280381 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PITPNM2	NM_020845.3	c.-96+19190T>C		intron_variant	Intron 2 of 25	ENST00000320201.10	NP_065896.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PITPNM2	ENST00000320201.10	c.-96+19190T>C		intron_variant	Intron 2 of 25	5	NM_020845.3	ENSP00000322218.4

Frequencies

GnomAD3 genomes AF: 0.692 AC: 105248 AN: 152052 Hom.: 36573 Cov.: 33

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.700

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.678

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.717

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.711

Gnomad OTH AF: 0.690

GnomAD4 exome AF: 0.500 AC: 7 AN: 14 Hom.: 2 Cov.: 0 AF XY: 0.500 AC XY: 4 AN XY: 8

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.625 AC: 5 AN: 8

Other (OTH) AF: 1.00 AC: 2 AN: 2

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000907115), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.692 AC: 105321 AN: 152170 Hom.: 36599 Cov.: 33 AF XY: 0.691 AC XY: 51418 AN XY: 74382

African (AFR) AF: 0.668 AC: 27731 AN: 41510

American (AMR) AF: 0.699 AC: 10692 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.636 AC: 2208 AN: 3472

East Asian (EAS) AF: 0.678 AC: 3500 AN: 5162

South Asian (SAS) AF: 0.606 AC: 2921 AN: 4822

European-Finnish (FIN) AF: 0.717 AC: 7602 AN: 10598

Middle Eastern (MID) AF: 0.613 AC: 179 AN: 292

European-Non Finnish (NFE) AF: 0.711 AC: 48357 AN: 67994

Other (OTH) AF: 0.687 AC: 1450 AN: 2110

Alfa AF: 0.697 Hom.: 111008

Bravo AF: 0.687

Asia WGS AF: 0.618 AC: 2150 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.051
DANN	Benign	0.44
PhyloP100		-2.8
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: rs1727307; hg19: chr12-123575742;