rs368162905

Variant names:

• chr1-98956617-C-A
• rs368162905
• NM_001037317.2:c.362G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-98956617-C-A
• chr1-98956617-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001037317.2(PLPPR5):​c.362G>T​(p.Arg121Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000701 in 1,425,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R121Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: PLPPR5 NM_001037317.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.94
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.8

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.362G>T	p.Arg121Leu	missense	Exon 2 of 6	NP_001032394.1	Q32ZL2-1
	PLPPR5	NM_001010861.3		c.362G>T	p.Arg121Leu	missense	Exon 2 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.362G>T	p.Arg121Leu	missense	Exon 2 of 6	ENSP00000263177.4	Q32ZL2-1
	PLPPR5	ENST00000370188.7	TSL:1	c.362G>T	p.Arg121Leu	missense	Exon 2 of 6	ENSP00000359207.3	Q32ZL2-2
	PLPPR5	ENST00000672681.1		c.362G>T	p.Arg121Leu	missense	Exon 2 of 7	ENSP00000500930.1	A0A5F9ZI76

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.01e-7 AC: 1 AN: 1425780 Hom.: 0 Cov.: 30 AF XY: 0.00000141 AC XY: 1 AN XY: 708436

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000320 AC: 1 AN: 31264

American (AMR) AF: 0.00 AC: 0 AN: 35954

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25226

East Asian (EAS) AF: 0.00 AC: 0 AN: 37984

South Asian (SAS) AF: 0.00 AC: 0 AN: 78224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52840

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1099686

Other (OTH) AF: 0.00 AC: 0 AN: 58910

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Pathogenic	0.71
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.091	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Uncertain	-0.24	T
PhyloP100		2.9
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Uncertain	0.45
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.98	D
Vest4		0.85
MutPred		0.59		Loss of methylation at R121 (P = 0.0253)
MVP		0.12
MPC		1.7
ClinPred		1.0	D
GERP RS		4.7
Varity_R		0.75
gMVP		0.95
Mutation Taster		=66/34	polymorphism

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

Other links and lift over

dbSNP: rs368162905; hg19: chr1-99422173; COSMIC: COSV99587127;