chr12-122986074-C-G

Variant names:

• chr12-122986074-C-G
• NM_020845.3:c.4003G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020845.3(PITPNM2):​c.4003G>C​(p.Ala1335Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000781 in 1,279,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign 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: 7.8e-7 (0 hom.)
• Consequence: PITPNM2 NM_020845.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.200

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07540092).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PITPNM2	NM_020845.3	c.4003G>C	p.Ala1335Pro	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.4003G>C	p.Ala1335Pro	missense_variant	Exon 26 of 26	5	NM_020845.3	ENSP00000322218.4
PITPNM2	ENST00000280562.9	c.3985G>C	p.Ala1329Pro	missense_variant	Exon 25 of 25	5		ENSP00000280562.5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.81e-7 AC: 1 AN: 1279814 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 626308

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: 0.00

Gnomad4 NFE exome AF: 9.65e-7

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	Benign	0.10
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.078	T;.;T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.39	N
LIST_S2	Uncertain	0.87	.;D;D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.075	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N;.;N
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.12
Sift	Benign	0.032	D;D;D
Sift4G	Uncertain	0.058	T;T;T
Polyphen		0.53	P;P;P
Vest4		0.19
MutPred		0.27		Gain of catalytic residue at W1332 (P = 0);.;Gain of catalytic residue at W1332 (P = 0);
MVP		0.14
MPC		1.7
ClinPred		0.46	T
GERP RS		-2.0
Varity_R		0.17
gMVP		0.34

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: chr12-123470621;