chr11-63463585-G-C

Variant names:

• chr11-63463585-G-C
• rs199651000
• NM_001146729.2:c.728C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001146729.2(PLAAT5):​c.728C>G​(p.Ala243Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,370 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign 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. A243D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PLAAT5 NM_001146729.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0620
• Publications: 2 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15899554).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAAT5	NM_001146729.2	MANE Select	c.728C>G	p.Ala243Gly	missense	Exon 6 of 6	NP_001140201.2	Q96KN8-3
	PLAAT5	NM_054108.4		c.758C>G	p.Ala253Gly	missense	Exon 6 of 6	NP_473449.2	Q96KN8-1
	PLAAT5	NM_001146728.2		c.708C>G	p.Arg236Arg	synonymous	Exon 6 of 6	NP_001140200.2	Q96KN8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAAT5	ENST00000540857.6	TSL:1 MANE Select	c.728C>G	p.Ala243Gly	missense	Exon 6 of 6	ENSP00000444809.1	Q96KN8-3
	PLAAT5	ENST00000301790.4	TSL:1	c.758C>G	p.Ala253Gly	missense	Exon 6 of 6	ENSP00000301790.4	Q96KN8-1
	PLAAT5	ENST00000539221.5	TSL:1	c.708C>G	p.Arg236Arg	synonymous	Exon 6 of 6	ENSP00000443873.1	Q96KN8-2

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152134 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461236 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726994

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

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52876

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111918

Other (OTH) AF: 0.0000166 AC: 1 AN: 60380

⚠️ 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 AF: 0.0000131 AC: 2 AN: 152134 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74310

African (AFR) AF: 0.00 AC: 0 AN: 41422

American (AMR) AF: 0.0000654 AC: 1 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.052	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.062
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.076
Sift	Benign	0.045	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.36	B
Vest4		0.25
MutPred		0.64		Gain of catalytic residue at A253 (P = 0.0014)
MVP		0.17
MPC		0.43
ClinPred		0.20	T
GERP RS		-2.0
Varity_R		0.084
gMVP		0.40
Mutation Taster		=96/4	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: rs199651000; hg19: chr11-63231057;