chr1-99004455-C-A

Position:

chr1-99004455-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001037317.2(PLPPR5):c.217G>T(p.Ala73Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000181 in 1,606,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

PLPPR5
NM_001037317.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.55

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 links:

PLPPR5-AS1 (HGNC:55720): (PLPPR5 antisense RNA 1)

PLPPR5-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.10307512).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PLPPR5	NM_001037317.2 linkuse as main transcript	c.217G>T	p.Ala73Ser	missense_variant	1/6	ENST00000263177.5	NP_001032394.1
PLPPR5-AS1	NR_033940.1 linkuse as main transcript	n.180C>A		non_coding_transcript_exon_variant	1/3
PLPPR5	NM_001010861.3 linkuse as main transcript	c.217G>T	p.Ala73Ser	missense_variant	1/6		NP_001010861.1
PLPPR5	XM_011540838.4 linkuse as main transcript	c.169G>T	p.Ala57Ser	missense_variant	2/7		XP_011539140.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLPPR5	ENST00000263177.5 linkuse as main transcript	c.217G>T	p.Ala73Ser	missense_variant	1/6	1	NM_001037317.2	ENSP00000263177	P4	Q32ZL2-1
PLPPR5-AS1	ENST00000658279.1 linkuse as main transcript	n.12C>A		non_coding_transcript_exon_variant	1/4

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

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:

0.000478

GnomAD3 exomes

AF:

0.0000168

AC:

AN:

237720

Hom.:

AF XY:

0.0000154

AC XY:

AN XY:

129972

show subpopulations

Gnomad AFR exome

AF:

0.000273

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1453710

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

722692

show subpopulations

Gnomad4 AFR exome

AF:

0.000362

Gnomad4 AMR exome

AF:

0.0000228

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000919

AC:

AN:

152324

Hom.:

Cov.:

AF XY:

0.0000805

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.000289

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:

0.000473

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000756

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Aug 02, 2021

The c.217G>T (p.A73S) alteration is located in exon 1 (coding exon 1) of the PLPPR5 gene. This alteration results from a G to T substitution at nucleotide position 217, causing the alanine (A) at amino acid position 73 to be replaced by a serine (S). 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

Benign

0.18

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.51

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.018

.;T

Eigen

Benign

-0.046

Eigen_PC

Benign

0.058

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.84

T;T

M_CAP

Benign

0.041

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.86

D;D

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.69

N;N

REVEL

Benign

0.074

Sift

Benign

0.40

T;T

Sift4G

Benign

0.18

T;T

Polyphen

0.26

B;B

Vest4

0.30

MutPred

0.54

Gain of glycosylation at A73 (P = 0.0054);Gain of glycosylation at A73 (P = 0.0054);

MVP

0.082

MPC

0.54

ClinPred

0.13

GERP RS

4.3

Varity_R

0.10

gMVP

0.62

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