NM_000929.3:c.9C>T

Variant names:

• chr1-20084839-C-T
• rs2020887
• NM_000929.3:c.9C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000929.3(PLA2G5):​c.9C>T​(p.Gly3Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 1,602,812 control chromosomes in the GnomAD database, including 91,725 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (6982 hom., cov: 31)
  • Exomes 𝑓: 0.34 (84743 hom.)
• Consequence: PLA2G5 NM_000929.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.214
• Publications: 18 publications found

Genes affected

PLA2G5 (HGNC:9038): (phospholipase A2 group V) This gene is a member of the secretory phospholipase A2 family. It is located in a tightly-linked cluster of secretory phospholipase A2 genes on chromosome 1. The encoded enzyme catalyzes the hydrolysis of membrane phospholipids to generate lysophospholipids and free fatty acids including arachidonic acid. It preferentially hydrolyzes linoleoyl-containing phosphatidylcholine substrates. Secretion of this enzyme is thought to induce inflammatory responses in neighboring cells. Alternatively spliced transcript variants have been found, but their full-length nature has not been determined. [provided by RefSeq, Jul 2008]

PLA2G5 Gene-Disease associations (from GenCC):

• familial benign flecked retina

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, G2P, Orphanet
• late-adult onset retinitis pigmentosa

  Inheritance: AR Classification: LIMITED Submitted by: Franklin by Genoox

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 1-20084839-C-T is Benign according to our data. Variant chr1-20084839-C-T is described in ClinVar as Benign. ClinVar VariationId is 1166519.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.214 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000929.3. 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
	PLA2G5	NM_000929.3	MANE Select	c.9C>T	p.Gly3Gly	synonymous	Exon 2 of 5	NP_000920.1	P39877

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G5	ENST00000375108.4	TSL:1 MANE Select	c.9C>T	p.Gly3Gly	synonymous	Exon 2 of 5	ENSP00000364249.3	P39877
	PLA2G5	ENST00000894073.1		c.9C>T	p.Gly3Gly	synonymous	Exon 4 of 7	ENSP00000564132.1
	PLA2G5	ENST00000894074.1		c.9C>T	p.Gly3Gly	synonymous	Exon 6 of 9	ENSP00000564133.1

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43342 AN: 151736 Hom.: 6974 Cov.: 31

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.298

GnomAD2 exomes AF: 0.325 AC: 81704 AN: 251322 AF XY: 0.334

Gnomad AFR exome AF: 0.121

Gnomad AMR exome AF: 0.232

Gnomad ASJ exome AF: 0.363

Gnomad EAS exome AF: 0.307

Gnomad FIN exome AF: 0.415

Gnomad NFE exome AF: 0.360

Gnomad OTH exome AF: 0.344

GnomAD4 exome AF: 0.337 AC: 488702 AN: 1450958 Hom.: 84743 Cov.: 30 AF XY: 0.339 AC XY: 244731 AN XY: 722518

African (AFR) AF: 0.119 AC: 3968 AN: 33342

American (AMR) AF: 0.240 AC: 10739 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 9433 AN: 26066

East Asian (EAS) AF: 0.316 AC: 12534 AN: 39648

South Asian (SAS) AF: 0.337 AC: 28959 AN: 85970

European-Finnish (FIN) AF: 0.418 AC: 22329 AN: 53406

Middle Eastern (MID) AF: 0.370 AC: 2119 AN: 5734

European-Non Finnish (NFE) AF: 0.344 AC: 378758 AN: 1102112

Other (OTH) AF: 0.331 AC: 19863 AN: 59978

GnomAD4 genome AF: 0.286 AC: 43372 AN: 151854 Hom.: 6982 Cov.: 31 AF XY: 0.286 AC XY: 21260 AN XY: 74208

African (AFR) AF: 0.122 AC: 5066 AN: 41422

American (AMR) AF: 0.276 AC: 4219 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 1245 AN: 3458

East Asian (EAS) AF: 0.318 AC: 1638 AN: 5152

South Asian (SAS) AF: 0.323 AC: 1556 AN: 4814

European-Finnish (FIN) AF: 0.410 AC: 4318 AN: 10536

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.356 AC: 24179 AN: 67904

Other (OTH) AF: 0.304 AC: 638 AN: 2100

Alfa AF: 0.326 Hom.: 15050

Bravo AF: 0.267

Asia WGS AF: 0.339 AC: 1175 AN: 3478

EpiCase AF: 0.353

EpiControl AF: 0.350

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	7.5
DANN	Benign	0.61
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs2020887; hg19: chr1-20411332; COSMIC: COSV64282882;