1-98956645-T-C

Position:

• chr1-98956645-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001037317.2(PLPPR5):​c.334A>G​(p.Ile112Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000483 in 1,449,592 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: PLPPR5 NM_001037317.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.986

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18635541).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLPPR5	NM_001037317.2	c.334A>G	p.Ile112Val	missense_variant	2/6	ENST00000263177.5	NP_001032394.1
PLPPR5	NM_001010861.3	c.334A>G	p.Ile112Val	missense_variant	2/6		NP_001010861.1
PLPPR5	XM_011540838.4	c.286A>G	p.Ile96Val	missense_variant	3/7		XP_011539140.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLPPR5	ENST00000263177.5	c.334A>G	p.Ile112Val	missense_variant	2/6	1	NM_001037317.2	ENSP00000263177	P4
PLPPR5	ENST00000370188.7	c.334A>G	p.Ile112Val	missense_variant	2/6	1		ENSP00000359207	A1
PLPPR5	ENST00000672681.1	c.334A>G	p.Ile112Val	missense_variant	2/7			ENSP00000500930
PLPPR5	ENST00000696571.1	c.169A>G	p.Ile57Val	missense_variant	3/7			ENSP00000512726

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000483 AC: 7 AN: 1449592 Hom.: 0 Cov.: 30 AF XY: 0.00000277 AC XY: 2 AN XY: 720824

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: 0.00000542

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 31

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

Jul 12, 2023

The c.334A>G (p.I112V) alteration is located in exon 2 (coding exon 2) of the PLPPR5 gene. This alteration results from a A to G substitution at nucleotide position 334, causing the isoleucine (I) at amino acid position 112 to be replaced by a valine (V). 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	0.14
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.014	.;T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.062
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.85	D;D
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.50	N;N
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.56	N;N
REVEL	Benign	0.055
Sift	Benign	0.47	T;T
Sift4G	Benign	0.50	T;T
Polyphen		0.0030	B;B
Vest4		0.26
MutPred		0.61		Loss of catalytic residue at P114 (P = 0.08);Loss of catalytic residue at P114 (P = 0.08);
MVP		0.043
MPC		0.49
ClinPred		0.39	T
GERP RS		4.7
Varity_R		0.12
gMVP		0.54

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-99422201;