12-122986208-C-T

Variant names:

• chr12-122986208-C-T
• rs1243446303
• NM_020845.3:c.3869G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_020845.3(PITPNM2):​c.3869G>A​(p.Arg1290Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000107 in 1,408,000 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: PITPNM2 NM_020845.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.33
• Publications: 1 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2316337).
• BS2: High AC in GnomAdExome4 at 15 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020845.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PITPNM2	NM_020845.3	MANE Select	c.3869G>A	p.Arg1290Gln	missense	Exon 26 of 26	NP_065896.1	Q9BZ72-1
	PITPNM2	NM_001384660.1		c.4046G>A	p.Arg1349Gln	missense	Exon 26 of 26	NP_001371589.1
	PITPNM2	NM_001300801.2		c.3851G>A	p.Arg1284Gln	missense	Exon 26 of 26	NP_001287730.1	Q9BZ72-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PITPNM2	ENST00000320201.10	TSL:5 MANE Select	c.3869G>A	p.Arg1290Gln	missense	Exon 26 of 26	ENSP00000322218.4	Q9BZ72-1
	PITPNM2	ENST00000876870.1		c.3869G>A	p.Arg1290Gln	missense	Exon 25 of 25	ENSP00000546929.1
	PITPNM2	ENST00000280562.9	TSL:5	c.3851G>A	p.Arg1284Gln	missense	Exon 25 of 25	ENSP00000280562.5	Q9BZ72-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000315 AC: 5 AN: 158704 AF XY: 0.0000344

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000770

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000311

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000107 AC: 15 AN: 1408000 Hom.: 0 Cov.: 31 AF XY: 0.0000144 AC XY: 10 AN XY: 696836

African (AFR) AF: 0.00 AC: 0 AN: 32588

American (AMR) AF: 0.0000805 AC: 3 AN: 37260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25274

East Asian (EAS) AF: 0.00 AC: 0 AN: 37390

South Asian (SAS) AF: 0.0000372 AC: 3 AN: 80672

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41256

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5666

European-Non Finnish (NFE) AF: 0.00000826 AC: 9 AN: 1089320

Other (OTH) AF: 0.00 AC: 0 AN: 58574

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.9	L
PhyloP100		3.3
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.12
Sift	Benign	0.27	T
Sift4G	Benign	0.16	T
Polyphen		1.0	D
Vest4		0.13
MutPred		0.40		Gain of catalytic residue at L1294 (P = 0.0045)
MVP		0.21
MPC		2.3
ClinPred		0.66	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.38
Mutation Taster		=53/47	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1243446303; hg19: chr12-123470755;