chr1-99004470-G-A

Variant summary

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

The NM_001037317.2(PLPPR5):​c.202C>T​(p.Leu68Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,611,638 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PLPPR5
NM_001037317.2 missense

Scores

2
9
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.39
Variant links:
Genes affected
PLPPR5 (HGNC:31703): (phospholipid phosphatase related 5) The protein encoded by this gene is a type 2 member of the phosphatidic acid phosphatase (PAP) family. All type 2 members of this protein family contain 6 transmembrane regions, and a consensus N-glycosylation site. PAPs convert phosphatidic acid to diacylglycerol, and function in de novo synthesis of glycerolipids as well as in receptor-activated signal transduction mediated by phospholipase D. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]
PLPPR5-AS1 (HGNC:55720): (PLPPR5 antisense RNA 1)

Genome browser will be placed here

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
PLPPR5NM_001037317.2 linkuse as main transcriptc.202C>T p.Leu68Phe missense_variant 1/6 ENST00000263177.5 NP_001032394.1
PLPPR5-AS1NR_033940.1 linkuse as main transcriptn.195G>A non_coding_transcript_exon_variant 1/3
PLPPR5NM_001010861.3 linkuse as main transcriptc.202C>T p.Leu68Phe missense_variant 1/6 NP_001010861.1
PLPPR5XM_011540838.4 linkuse as main transcriptc.154C>T p.Leu52Phe missense_variant 2/7 XP_011539140.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PLPPR5ENST00000263177.5 linkuse as main transcriptc.202C>T p.Leu68Phe missense_variant 1/61 NM_001037317.2 ENSP00000263177 P4Q32ZL2-1
PLPPR5-AS1ENST00000658279.1 linkuse as main transcriptn.27G>A non_coding_transcript_exon_variant 1/4

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152238
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.00
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1459400
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
725960
show subpopulations
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:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152238
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74376
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
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:
0.00
Bravo
AF:
0.00000378

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 submitterclinical testingAmbry GeneticsMar 31, 2023The c.202C>T (p.L68F) alteration is located in exon 1 (coding exon 1) of the PLPPR5 gene. This alteration results from a C to T substitution at nucleotide position 202, causing the leucine (L) at amino acid position 68 to be replaced by a phenylalanine (F). 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
0.77
BayesDel_addAF
Benign
-0.027
T
BayesDel_noAF
Benign
-0.28
CADD
Pathogenic
31
DANN
Uncertain
1.0
DEOGEN2
Benign
0.22
.;T
Eigen
Uncertain
0.64
Eigen_PC
Uncertain
0.58
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Uncertain
0.94
D;D
M_CAP
Uncertain
0.18
D
MetaRNN
Uncertain
0.48
T;T
MetaSVM
Benign
-0.62
T
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.84
D
PROVEAN
Uncertain
-2.5
D;D
REVEL
Benign
0.25
Sift
Uncertain
0.0030
D;D
Sift4G
Benign
0.12
T;T
Polyphen
0.99
D;D
Vest4
0.54
MutPred
0.43
Gain of catalytic residue at L68 (P = 0.0135);Gain of catalytic residue at L68 (P = 0.0135);
MVP
0.13
MPC
1.6
ClinPred
0.99
D
GERP RS
4.2
Varity_R
0.57
gMVP
0.79

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.

Other links and lift over

dbSNP: rs1169467689; hg19: chr1-99470026; API