12-123000641-A-G

Variant names:

• chr12-123000641-A-G
• rs883263
• NM_020845.3:c.1224+137T>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.1224+137T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 1,000,078 control chromosomes in the GnomAD database, including 307,244 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 0.78 (46112 hom., cov: 33)
  • Exomes 𝑓: 0.78 (261132 hom.)
• Consequence: PITPNM2 NM_020845.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 19 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PITPNM2	NM_020845.3	c.1224+137T>C		intron_variant	Intron 10 of 25	ENST00000320201.10	NP_065896.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PITPNM2	ENST00000320201.10	c.1224+137T>C		intron_variant	Intron 10 of 25	5	NM_020845.3	ENSP00000322218.4

Frequencies

GnomAD3 genomes AF: 0.777 AC: 118169 AN: 152066 Hom.: 46064 Cov.: 33

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.779

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.862

Gnomad SAS AF: 0.744

Gnomad FIN AF: 0.813

Gnomad MID AF: 0.650

Gnomad NFE AF: 0.787

Gnomad OTH AF: 0.777

GnomAD4 exome AF: 0.784 AC: 664739 AN: 847894 Hom.: 261132 Cov.: 11 AF XY: 0.782 AC XY: 338060 AN XY: 432508

African (AFR) AF: 0.752 AC: 15736 AN: 20912

American (AMR) AF: 0.732 AC: 22807 AN: 31158

Ashkenazi Jewish (ASJ) AF: 0.703 AC: 13355 AN: 19000

East Asian (EAS) AF: 0.869 AC: 28823 AN: 33162

South Asian (SAS) AF: 0.748 AC: 45937 AN: 61428

European-Finnish (FIN) AF: 0.817 AC: 29590 AN: 36204

Middle Eastern (MID) AF: 0.706 AC: 3176 AN: 4498

European-Non Finnish (NFE) AF: 0.788 AC: 474132 AN: 601692

Other (OTH) AF: 0.783 AC: 31183 AN: 39840

GnomAD4 genome AF: 0.777 AC: 118271 AN: 152184 Hom.: 46112 Cov.: 33 AF XY: 0.778 AC XY: 57926 AN XY: 74410

African (AFR) AF: 0.751 AC: 31189 AN: 41518

American (AMR) AF: 0.778 AC: 11907 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 2385 AN: 3472

East Asian (EAS) AF: 0.862 AC: 4461 AN: 5178

South Asian (SAS) AF: 0.744 AC: 3584 AN: 4816

European-Finnish (FIN) AF: 0.813 AC: 8619 AN: 10604

Middle Eastern (MID) AF: 0.647 AC: 189 AN: 292

European-Non Finnish (NFE) AF: 0.787 AC: 53518 AN: 67984

Other (OTH) AF: 0.779 AC: 1646 AN: 2112

Alfa AF: 0.775 Hom.: 17140

Bravo AF: 0.772

Asia WGS AF: 0.802 AC: 2789 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.16
DANN	Benign	0.35
PhyloP100		-1.1
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: rs883263; hg19: chr12-123485188;