11-63466238-A-G

Variant names:

• chr11-63466238-A-G
• rs2275999
• NM_001146729.2:c.589T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146729.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAAT5	NM_001146729.2	MANE Select	c.589T>C	p.Leu197Leu	synonymous	Exon 5 of 6	NP_001140201.2
	PLAAT5	NM_054108.4		c.619T>C	p.Leu207Leu	synonymous	Exon 5 of 6	NP_473449.2
	PLAAT5	NM_001146728.2		c.619T>C	p.Leu207Leu	synonymous	Exon 5 of 6	NP_001140200.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAAT5	ENST00000540857.6	TSL:1 MANE Select	c.589T>C	p.Leu197Leu	synonymous	Exon 5 of 6	ENSP00000444809.1
	PLAAT5	ENST00000301790.4	TSL:1	c.619T>C	p.Leu207Leu	synonymous	Exon 5 of 6	ENSP00000301790.4
	PLAAT5	ENST00000539221.5	TSL:1	c.619T>C	p.Leu207Leu	synonymous	Exon 5 of 6	ENSP00000443873.1

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

GnomAD2 exomes AF: 0.136 AC: 34184 AN: 251372 AF XY: 0.128

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 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

African (AFR) AF: 0.355 AC: 11898 AN: 33476

American (AMR) AF: 0.233 AC: 10438 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0613 AC: 1603 AN: 26136

East Asian (EAS) AF: 0.174 AC: 6912 AN: 39700

South Asian (SAS) AF: 0.185 AC: 15922 AN: 86258

European-Finnish (FIN) AF: 0.134 AC: 7167 AN: 53420

Middle Eastern (MID) AF: 0.0856 AC: 494 AN: 5768

European-Non Finnish (NFE) AF: 0.0669 AC: 74389 AN: 1111998

Other (OTH) AF: 0.109 AC: 6586 AN: 60394

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

African (AFR) AF: 0.341 AC: 14131 AN: 41432

American (AMR) AF: 0.181 AC: 2765 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0568 AC: 197 AN: 3470

East Asian (EAS) AF: 0.174 AC: 898 AN: 5166

South Asian (SAS) AF: 0.197 AC: 948 AN: 4824

European-Finnish (FIN) AF: 0.150 AC: 1586 AN: 10574

Middle Eastern (MID) AF: 0.0788 AC: 23 AN: 292

European-Non Finnish (NFE) AF: 0.0647 AC: 4403 AN: 68020

Other (OTH) AF: 0.159 AC: 335 AN: 2110

Alfa AF: 0.0964 Hom.: 1982

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	4.6
DANN	Benign	0.63
PhyloP100		3.0
Mutation Taster		=100/0	polymorphism (auto)

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