Variant 9-101270039-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_207299.2(PLPPR1):c.223T>C(p.Cys75Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000131 in 152,186 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Consequence

PLPPR1
NM_207299.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.08

Variant links:

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]

PLPPR1 links:

PLPPR1 (HGNC:):

PLPPR1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLPPR1	NM_207299.2 linkuse as main transcript	c.223T>C	p.Cys75Arg	missense_variant	3/8	ENST00000374874.8	NP_997182.1	Q8TBJ4A0A024R154
PLPPR1	NM_017753.3 linkuse as main transcript	c.223T>C	p.Cys75Arg	missense_variant	3/8		NP_060223.2	Q8TBJ4A0A024R154

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PLPPR1	ENST00000374874.8 linkuse as main transcript	c.223T>C	p.Cys75Arg	missense_variant	3/8	1	NM_207299.2	ENSP00000364008.3	Q8TBJ4
PLPPR1	ENST00000395056.2 linkuse as main transcript	c.223T>C	p.Cys75Arg	missense_variant	3/8	1		ENSP00000378496.1	Q8TBJ4
PLPPR1	ENST00000456287.5 linkuse as main transcript	c.223T>C	p.Cys75Arg	missense_variant	3/4	3		ENSP00000410223.1	M9MML5
PLPPR1	ENST00000463206.1 linkuse as main transcript	n.238T>C		non_coding_transcript_exon_variant	1/4	3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000479

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 08, 2024

The c.223T>C (p.C75R) alteration is located in exon 3 (coding exon 2) of the PLPPR1 gene. This alteration results from a T to C substitution at nucleotide position 223, causing the cysteine (C) at amino acid position 75 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;.;T

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.84

.;T;T

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.65

D;D;D

MetaSVM

Benign

-1.0

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-1.9

N;N;N

REVEL

Uncertain

0.34

Sift

Benign

0.054

T;T;T

Sift4G

Benign

0.16

T;D;T

Polyphen

0.99

D;.;D

Vest4

0.95

MutPred

0.57

Gain of glycosylation at T80 (P = 0.1199);Gain of glycosylation at T80 (P = 0.1199);Gain of glycosylation at T80 (P = 0.1199);

MVP

0.57

MPC

1.9

ClinPred

0.93

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.68

gMVP

0.97

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over