chr11-63466238-A-G

Position:

• chr11-63466238-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001146729.2(PLAAT5):​c.589T>C​(p.Leu197Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0996 in 1,613,952 control chromosomes in the GnomAD database, including 12,587 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 0.17 (3317 hom., cov: 31)
  • Exomes 𝑓: 0.093 (9270 hom.)
• Consequence: PLAAT5 NM_001146729.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.05

Genes affected

PLAAT5 (HGNC:24978): (phospholipase A and acyltransferase 5) Enables N-acyltransferase activity; phospholipase A1 activity; and phospholipase A2 activity. Acts upstream of or within N-acylphosphatidylethanolamine metabolic process. Predicted to be located in cytosol. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP7: Synonymous conserved (PhyloP=3.05 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLAAT5	NM_001146729.2	c.589T>C	p.Leu197Leu	synonymous_variant	5/6	ENST00000540857.6	NP_001140201.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLAAT5	ENST00000540857.6	c.589T>C	p.Leu197Leu	synonymous_variant	5/6	1	NM_001146729.2	ENSP00000444809.1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25365 AN: 151960 Hom.: 3308 Cov.: 31

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.0568

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.0828

Gnomad NFE AF: 0.0647

Gnomad OTH AF: 0.155

GnomAD3 exomes AF: 0.136 AC: 34184 AN: 251372 Hom.: 3388 AF XY: 0.128 AC XY: 17347 AN XY: 135864

Gnomad AFR exome AF: 0.349

Gnomad AMR exome AF: 0.233

Gnomad ASJ exome AF: 0.0601

Gnomad EAS exome AF: 0.168

Gnomad SAS exome AF: 0.184

Gnomad FIN exome AF: 0.139

Gnomad NFE exome AF: 0.0650

Gnomad OTH exome AF: 0.115

GnomAD4 exome AF: 0.0926 AC: 135409 AN: 1461874 Hom.: 9270 Cov.: 33 AF XY: 0.0930 AC XY: 67653 AN XY: 727244

Gnomad4 AFR exome AF: 0.355

Gnomad4 AMR exome AF: 0.233

Gnomad4 ASJ exome AF: 0.0613

Gnomad4 EAS exome AF: 0.174

Gnomad4 SAS exome AF: 0.185

Gnomad4 FIN exome AF: 0.134

Gnomad4 NFE exome AF: 0.0669

Gnomad4 OTH exome AF: 0.109

GnomAD4 genome AF: 0.167 AC: 25404 AN: 152078 Hom.: 3317 Cov.: 31 AF XY: 0.169 AC XY: 12588 AN XY: 74338

Gnomad4 AFR AF: 0.341

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.0568

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.0647

Gnomad4 OTH AF: 0.159

Alfa AF: 0.0851 Hom.: 1244

Bravo AF: 0.180

Asia WGS AF: 0.180 AC: 623 AN: 3478

EpiCase AF: 0.0647

EpiControl AF: 0.0647

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	4.6
DANN	Benign	0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs2275999; hg19: chr11-63233710; COSMIC: COSV57137045; COSMIC: COSV57137045;