chr1-98956690-A-G

Position:

• chr1-98956690-A-G

Variant summary

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

The NM_001037317.2(PLPPR5):​c.289T>C​(p.Phe97Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: PLPPR5 NM_001037317.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.49

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=0.11002809).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLPPR5	NM_001037317.2	c.289T>C	p.Phe97Leu	missense_variant	2/6	ENST00000263177.5
PLPPR5	NM_001010861.3	c.289T>C	p.Phe97Leu	missense_variant	2/6
PLPPR5	XM_011540838.4	c.241T>C	p.Phe81Leu	missense_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLPPR5	ENST00000263177.5	c.289T>C	p.Phe97Leu	missense_variant	2/6	1	NM_001037317.2	P4
PLPPR5	ENST00000370188.7	c.289T>C	p.Phe97Leu	missense_variant	2/6	1		A1
PLPPR5	ENST00000672681.1	c.289T>C	p.Phe97Leu	missense_variant	2/7
PLPPR5	ENST00000696571.1	c.124T>C	p.Phe42Leu	missense_variant	3/7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

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

May 13, 2024

The c.289T>C (p.F97L) alteration is located in exon 2 (coding exon 2) of the PLPPR5 gene. This alteration results from a T to C substitution at nucleotide position 289, causing the phenylalanine (F) at amino acid position 97 to be replaced by a leucine (L). 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	0.69
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	21
DANN	Benign	0.91
DEOGEN2	Benign	0.0028	.;T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.56	D;D
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	0.14	N;N
REVEL	Benign	0.083
Sift	Benign	0.67	T;T
Sift4G	Benign	0.72	T;T
Polyphen		0.0010	B;B
Vest4		0.46
MutPred		0.33		Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);
MVP		0.043
MPC		0.69
ClinPred		0.84	D
GERP RS		4.7
Varity_R		0.17
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr1-99422246;