rs1017607614

Variant names:

• chr12-122986118-C-G
• rs1017607614
• NM_020845.3:c.3959G>C

Your query was ambiguous. Multiple possible variants found:

• chr12-122986118-C-G
• chr12-122986118-C-A
• chr12-122986118-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Moderate BS2

The NM_020845.3(PITPNM2):​c.3959G>C​(p.Arg1320Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000037 in 1,350,110 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: 34)
  • Exomes 𝑓: 0.0000037 (0 hom.)
• Consequence: PITPNM2 NM_020845.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.52
• Publications: 0 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16938162).
• BS2: High AC in GnomAdExome4 at 5 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.3959G>C	p.Arg1320Pro	missense	Exon 26 of 26	NP_065896.1	Q9BZ72-1
	PITPNM2	NM_001384660.1		c.4136G>C	p.Arg1379Pro	missense	Exon 26 of 26	NP_001371589.1
	PITPNM2	NM_001300801.2		c.3941G>C	p.Arg1314Pro	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.3959G>C	p.Arg1320Pro	missense	Exon 26 of 26	ENSP00000322218.4	Q9BZ72-1
	PITPNM2	ENST00000876870.1		c.3959G>C	p.Arg1320Pro	missense	Exon 25 of 25	ENSP00000546929.1
	PITPNM2	ENST00000280562.9	TSL:5	c.3941G>C	p.Arg1314Pro	missense	Exon 25 of 25	ENSP00000280562.5	Q9BZ72-2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000370 AC: 5 AN: 1350110 Hom.: 0 Cov.: 31 AF XY: 0.00000301 AC XY: 2 AN XY: 665004

African (AFR) AF: 0.00 AC: 0 AN: 27746

American (AMR) AF: 0.00 AC: 0 AN: 30746

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23716

East Asian (EAS) AF: 0.00 AC: 0 AN: 32700

South Asian (SAS) AF: 0.0000532 AC: 4 AN: 75202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4442

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1064998

Other (OTH) AF: 0.0000178 AC: 1 AN: 56168

GnomAD4 genome Cov.: 34

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	0.19
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.074	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.5
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.14
Sift	Benign	0.24	T
Sift4G	Benign	0.29	T
Polyphen		0.84	P
Vest4		0.19
MutPred		0.27		Loss of MoRF binding (P = 0.001)
MVP		0.54
MPC		2.5
ClinPred		0.88	D
GERP RS		4.8
Varity_R		0.29
gMVP		0.41
Mutation Taster		=57/43	polymorphism

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: rs1017607614; hg19: chr12-123470665;