1-98914920-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001037317.2(PLPPR5):c.799G>A(p.Val267Ile) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000686 in 1,457,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PLPPR5 NM_001037317.2 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.75

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41132495).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLPPR5	NM_001037317.2	c.799G>A	p.Val267Ile	missense_variant, splice_region_variant	5/6	ENST00000263177.5
PLPPR5	NM_001010861.3	c.799G>A	p.Val267Ile	missense_variant, splice_region_variant	5/6
PLPPR5	XM_011540838.4	c.751G>A	p.Val251Ile	missense_variant, splice_region_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLPPR5	ENST00000263177.5	c.799G>A	p.Val267Ile	missense_variant, splice_region_variant	5/6	1	NM_001037317.2	P4
PLPPR5	ENST00000370188.7	c.799G>A	p.Val267Ile	missense_variant, splice_region_variant	5/6	1		A1
PLPPR5	ENST00000672681.1	c.799G>A	p.Val267Ile	missense_variant, splice_region_variant	5/7
PLPPR5	ENST00000696571.1	c.634G>A	p.Val212Ile	missense_variant, splice_region_variant	6/7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457072 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725004

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 Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 30, 2024

The c.799G>A (p.V267I) alteration is located in exon 5 (coding exon 5) of the PLPPR5 gene. This alteration results from a G to A substitution at nucleotide position 799, causing the valine (V) at amino acid position 267 to be replaced by an isoleucine (I). 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	Uncertain	0.48
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Benign	-0.18
Cadd	Pathogenic	26
Dann	Uncertain	1.0
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.41	T;T
MetaSVM	Uncertain	0.084	D
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.85	N;N
REVEL	Uncertain	0.47
Sift	Benign	0.059	T;T
Sift4G	Benign	0.19	T;T
Polyphen		0.92	P;D
Vest4		0.37
MutPred		0.64		Loss of catalytic residue at V267 (P = 0.1617);Loss of catalytic residue at V267 (P = 0.1617);
MVP		0.31
MPC		0.46
ClinPred		0.96	D
GERP RS		6.0
Varity_R		0.17
gMVP		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-99380476;