12-122985100-G-T

Variant names:

• chr12-122985100-G-T
• rs3741530
• NM_020845.3:c.*927C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 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=-0.57).
• 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 rank	MANE	Protein	UniProt
PITPNM2	NM_020845.3	c.*927C>A		3_prime_UTR_variant	Exon 26 of 26	ENST00000320201.10	NP_065896.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PITPNM2	ENST00000320201.10	c.*927C>A		3_prime_UTR_variant	Exon 26 of 26	5	NM_020845.3	ENSP00000322218.4
PITPNM2	ENST00000280562.9	c.*927C>A		3_prime_UTR_variant	Exon 25 of 25	5		ENSP00000280562.5

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.744 AC: 247 AN: 332

Middle Eastern (MID) AC: 0 AN: 0

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

Other (OTH) AF: 0.500 AC: 1 AN: 2

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

African (AFR) AF: 0.151 AC: 6271 AN: 41516

American (AMR) AF: 0.637 AC: 9740 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.619 AC: 2148 AN: 3468

East Asian (EAS) AF: 0.673 AC: 3482 AN: 5176

South Asian (SAS) AF: 0.577 AC: 2781 AN: 4822

European-Finnish (FIN) AF: 0.718 AC: 7586 AN: 10566

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.707 AC: 48094 AN: 67986

Other (OTH) AF: 0.576 AC: 1215 AN: 2110

Alfa AF: 0.479 Hom.: 2433

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
PhyloP100		2.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3741530; hg19: chr12-123469647;