chr1-98953091-G-C

Variant names:

• chr1-98953091-G-C
• rs309087
• NM_001037317.2:c.600C>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001037317.2(PLPPR5):​c.600C>G​(p.Val200Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 1,613,384 control chromosomes in the GnomAD database, including 28,134 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (3427 hom., cov: 32)
  • Exomes 𝑓: 0.18 (24707 hom.)
• Consequence: PLPPR5 NM_001037317.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.586
• Publications: 14 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=0.586 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLPPR5	NM_001037317.2	c.600C>G	p.Val200Val	synonymous_variant	Exon 3 of 6	ENST00000263177.5	NP_001032394.1
PLPPR5	NM_001010861.3	c.600C>G	p.Val200Val	synonymous_variant	Exon 3 of 6		NP_001010861.1
PLPPR5	XM_011540838.4	c.552C>G	p.Val184Val	synonymous_variant	Exon 4 of 7		XP_011539140.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLPPR5	ENST00000263177.5	c.600C>G	p.Val200Val	synonymous_variant	Exon 3 of 6	1	NM_001037317.2	ENSP00000263177.4
PLPPR5	ENST00000370188.7	c.600C>G	p.Val200Val	synonymous_variant	Exon 3 of 6	1		ENSP00000359207.3
PLPPR5	ENST00000672681.1	c.600C>G	p.Val200Val	synonymous_variant	Exon 3 of 7			ENSP00000500930.1
PLPPR5	ENST00000696571.1	c.435C>G	p.Val145Val	synonymous_variant	Exon 4 of 7			ENSP00000512726.1

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31198 AN: 151932 Hom.: 3419 Cov.: 32

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.0824

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.197

GnomAD2 exomes AF: 0.192 AC: 48140 AN: 251072 AF XY: 0.194

Gnomad AFR exome AF: 0.268

Gnomad AMR exome AF: 0.152

Gnomad ASJ exome AF: 0.148

Gnomad EAS exome AF: 0.228

Gnomad FIN exome AF: 0.200

Gnomad NFE exome AF: 0.178

Gnomad OTH exome AF: 0.180

GnomAD4 exome AF: 0.181 AC: 263954 AN: 1461334 Hom.: 24707 Cov.: 34 AF XY: 0.183 AC XY: 132844 AN XY: 726998

African (AFR) AF: 0.275 AC: 9212 AN: 33466

American (AMR) AF: 0.154 AC: 6890 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 3970 AN: 26128

East Asian (EAS) AF: 0.223 AC: 8845 AN: 39660

South Asian (SAS) AF: 0.236 AC: 20392 AN: 86254

European-Finnish (FIN) AF: 0.193 AC: 10324 AN: 53378

Middle Eastern (MID) AF: 0.225 AC: 1295 AN: 5760

European-Non Finnish (NFE) AF: 0.172 AC: 191656 AN: 1111594

Other (OTH) AF: 0.188 AC: 11370 AN: 60376

GnomAD4 genome AF: 0.205 AC: 31232 AN: 152050 Hom.: 3427 Cov.: 32 AF XY: 0.206 AC XY: 15304 AN XY: 74316

African (AFR) AF: 0.274 AC: 11358 AN: 41470

American (AMR) AF: 0.155 AC: 2366 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 518 AN: 3470

East Asian (EAS) AF: 0.222 AC: 1149 AN: 5166

South Asian (SAS) AF: 0.230 AC: 1110 AN: 4816

European-Finnish (FIN) AF: 0.199 AC: 2102 AN: 10560

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12050 AN: 67982

Other (OTH) AF: 0.203 AC: 429 AN: 2112

Alfa AF: 0.181 Hom.: 2022

Bravo AF: 0.204

Asia WGS AF: 0.227 AC: 787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	6.9
DANN	Benign	0.76
PhyloP100		0.59
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs309087; hg19: chr1-99418647; COSMIC: COSV54173258;