chr1-98914920-C-T

Variant names:

• chr1-98914920-C-T
• NM_001037317.2:c.799G>A

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037317.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLPPR5	NM_001037317.2	MANE Select	c.799G>A	p.Val267Ile	missense splice_region	Exon 5 of 6	NP_001032394.1	Q32ZL2-1
	PLPPR5	NM_001010861.3		c.799G>A	p.Val267Ile	missense splice_region	Exon 5 of 6	NP_001010861.1	Q32ZL2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLPPR5	ENST00000263177.5	TSL:1 MANE Select	c.799G>A	p.Val267Ile	missense splice_region	Exon 5 of 6	ENSP00000263177.4	Q32ZL2-1
	PLPPR5	ENST00000370188.7	TSL:1	c.799G>A	p.Val267Ile	missense splice_region	Exon 5 of 6	ENSP00000359207.3	Q32ZL2-2
	PLPPR5	ENST00000672681.1		c.799G>A	p.Val267Ile	missense splice_region	Exon 5 of 7	ENSP00000500930.1	A0A5F9ZI76

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

African (AFR) AF: 0.00 AC: 0 AN: 33398

American (AMR) AF: 0.00 AC: 0 AN: 44486

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26054

East Asian (EAS) AF: 0.00 AC: 0 AN: 39606

South Asian (SAS) AF: 0.00 AC: 0 AN: 86024

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111126

Other (OTH) AF: 0.00 AC: 0 AN: 60292

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
DEOGEN2	Uncertain	0.46	T
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.41	T
MetaSVM	Uncertain	0.084	D
PhyloP100		6.8
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.85	N
REVEL	Uncertain	0.47
Sift	Benign	0.059	T
Sift4G	Benign	0.19	T
Polyphen		0.92	P
Vest4		0.37
MutPred		0.64		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
Mutation Taster		=57/43	polymorphism

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

Other links and lift over

hg19: chr1-99380476;