rs140912404

Variant names:

• chr9-101324035-C-A
• rs140912404
• NM_207299.2:c.956C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-101324035-C-A
• chr9-101324035-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_207299.2(PLPPR1):​c.956C>A​(p.Ala319Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,460,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A319V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PLPPR1 NM_207299.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.08
• Publications: 0 publications found

Genes affected

PLPPR1 (HGNC:25993): (phospholipid phosphatase related 1) This gene encodes a member of the plasticity-related gene (PRG) family. Members of the PRG family mediate lipid phosphate phosphatase activity in neurons and are known to be involved in neuronal plasticity. The protein encoded by this gene does not perform its function through enzymatic phospholipid degradation. This gene is strongly expressed in brain. It shows dynamic expression regulation during brain development and neuronal excitation. Alternatively spliced transcript variants encoding the same protein have been observed. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15587458).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207299.2. 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
	PLPPR1	NM_207299.2	MANE Select	c.956C>A	p.Ala319Glu	missense	Exon 8 of 8	NP_997182.1	Q8TBJ4
	PLPPR1	NM_017753.3		c.956C>A	p.Ala319Glu	missense	Exon 8 of 8	NP_060223.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLPPR1	ENST00000374874.8	TSL:1 MANE Select	c.956C>A	p.Ala319Glu	missense	Exon 8 of 8	ENSP00000364008.3	Q8TBJ4
	PLPPR1	ENST00000395056.2	TSL:1	c.956C>A	p.Ala319Glu	missense	Exon 8 of 8	ENSP00000378496.1	Q8TBJ4
	PLPPR1	ENST00000883514.1		c.956C>A	p.Ala319Glu	missense	Exon 8 of 8	ENSP00000553573.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460412 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726488

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 86172

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1110852

Other (OTH) AF: 0.00 AC: 0 AN: 60310

GnomAD4 genome Cov.: 32

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	0.32
BayesDel_addAF	Uncertain	0.044	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.012
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
PhyloP100		6.1
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.15
Sift	Benign	0.034	D
Sift4G	Uncertain	0.055	T
Polyphen		0.19	B
Vest4		0.48
MutPred		0.10		Gain of phosphorylation at S320 (P = 0.109)
MVP		0.23
MPC		0.75
ClinPred		0.92	D
GERP RS		5.2
Varity_R		0.21
gMVP		0.55
Mutation Taster		=59/41	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs140912404; hg19: chr9-104086317;