rs771095588

Variant names:

• chr11-63490994-C-T
• rs771095588
• NM_001146729.2:c.41G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001146729.2(PLAAT5):​c.41G>A​(p.Arg14His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00027 in 1,549,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R14S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00029 (0 hom.)
• Consequence: PLAAT5 NM_001146729.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.35
• Publications: 0 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]

ENSG00000287412 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.045862257).

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.41G>A	p.Arg14His	missense	Exon 1 of 6	NP_001140201.2	Q96KN8-3
	PLAAT5	NM_054108.4		c.41G>A	p.Arg14His	missense	Exon 1 of 6	NP_473449.2	Q96KN8-1
	PLAAT5	NM_001146728.2		c.41G>A	p.Arg14His	missense	Exon 1 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.41G>A	p.Arg14His	missense	Exon 1 of 6	ENSP00000444809.1	Q96KN8-3
	PLAAT5	ENST00000301790.4	TSL:1	c.41G>A	p.Arg14His	missense	Exon 1 of 6	ENSP00000301790.4	Q96KN8-1
	PLAAT5	ENST00000539221.5	TSL:1	c.41G>A	p.Arg14His	missense	Exon 1 of 6	ENSP00000443873.1	Q96KN8-2

Frequencies

GnomAD3 genomes AF: 0.0000855 AC: 13 AN: 152122 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000191

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000110 AC: 16 AN: 144874 AF XY: 0.0000893

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000278

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000291 AC: 406 AN: 1396974 Hom.: 0 Cov.: 33 AF XY: 0.000266 AC XY: 184 AN XY: 690920

African (AFR) AF: 0.000196 AC: 6 AN: 30586

American (AMR) AF: 0.00 AC: 0 AN: 35692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23578

East Asian (EAS) AF: 0.00 AC: 0 AN: 35398

South Asian (SAS) AF: 0.00 AC: 0 AN: 78886

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5236

European-Non Finnish (NFE) AF: 0.000361 AC: 390 AN: 1080544

Other (OTH) AF: 0.000173 AC: 10 AN: 57676

GnomAD4 genome AF: 0.0000855 AC: 13 AN: 152122 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74298

African (AFR) AF: 0.00 AC: 0 AN: 41436

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

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

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000209 Hom.: 0

Bravo AF: 0.0000642

ExAC AF: 0.0000766 AC: 9

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	6.4
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0034	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		-1.4
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.10
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.069	T
Polyphen		0.92	P
Vest4		0.041
MVP		0.23
MPC		0.15
ClinPred		0.091	T
GERP RS		-4.0
PromoterAI		-0.13	Neutral
Varity_R		0.051
gMVP		0.22
Mutation Taster		=100/0	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: rs771095588; hg19: chr11-63258466; COSMIC: COSV100080391; COSMIC: COSV100080391;