rs1179506363

Variant names:

• chr12-122986268-C-A
• NM_020845.3:c.3809G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-122986268-C-A
• chr12-122986268-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_020845.3(PITPNM2):​c.3809G>T​(p.Arg1270Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000699 in 1,429,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: PITPNM2 NM_020845.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.67

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.784

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PITPNM2	NM_020845.3	c.3809G>T	p.Arg1270Leu	missense_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.3809G>T	p.Arg1270Leu	missense_variant	Exon 26 of 26	5	NM_020845.3	ENSP00000322218.4
PITPNM2	ENST00000280562.9	c.3791G>T	p.Arg1264Leu	missense_variant	Exon 25 of 25	5		ENSP00000280562.5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.99e-7 AC: 1 AN: 1429618 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 709126

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000224

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.64	D;.;D
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	.;D;D
M_CAP	Benign	0.082	D
MetaRNN	Pathogenic	0.78	D;D;D
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Pathogenic	2.9	M;.;M
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-5.5	D;D;D
REVEL	Pathogenic	0.66
Sift	Uncertain	0.023	D;D;D
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.77
MutPred		0.53		Gain of catalytic residue at L1273 (P = 0.008);.;Gain of catalytic residue at L1273 (P = 0.008);
MVP		0.40
MPC		2.4
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.46
gMVP		0.75

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-123470815;