Genetic Variant NM_001146729.2:c.247G>C (chr11-63488969-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001146729.2(PLAAT5):c.247G>C(p.Ala83Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0719 in 1,606,038 control chromosomes in the GnomAD database, including 14,134 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.19 ( 6492 hom., cov: 32)

Exomes 𝑓: 0.060 ( 7642 hom. )

Consequence

PLAAT5
NM_001146729.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.432

Publications

14 publications found

Variant links:

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]

PLAAT5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.247038E-5).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLAAT5	NM_001146729.2 link	c.247G>C	p.Ala83Pro	missense_variant	Exon 3 of 6	ENST00000540857.6	NP_001140201.2	Q8NE88

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLAAT5	ENST00000540857.6 link	c.247G>C	p.Ala83Pro	missense_variant	Exon 3 of 6	1	NM_001146729.2	ENSP00000444809.1		Q96KN8-3

Frequencies

GnomAD3 genomes

AF:

0.190

AC:

28889

AN:

151852

Hom.:

6462

Cov.:

show subpopulations

Gnomad AFR

AF:

0.545

Gnomad AMI

AF:

0.0296

Gnomad AMR

AF:

0.0921

Gnomad ASJ

AF:

0.0652

Gnomad EAS

AF:

0.158

Gnomad SAS

AF:

0.0360

Gnomad FIN

AF:

0.0525

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0423

Gnomad OTH

AF:

0.143

GnomAD2 exomes

AF:

0.0860

AC:

21511

AN:

250200

AF XY:

0.0747

show subpopulations

Gnomad AFR exome

AF:

0.556

Gnomad AMR exome

AF:

0.0471

Gnomad ASJ exome

AF:

0.0662

Gnomad EAS exome

AF:

0.162

Gnomad FIN exome

AF:

0.0472

Gnomad NFE exome

AF:

0.0421

Gnomad OTH exome

AF:

0.0653

GnomAD4 exome

AF:

0.0595

AC:

86562

AN:

1454068

Hom.:

7642

Cov.:

AF XY:

0.0568

AC XY:

41127

AN XY:

723830

show subpopulations

African (AFR)

AF:

0.570

AC:

18830

AN:

33024

American (AMR)

AF:

0.0523

AC:

2326

AN:

44492

Ashkenazi Jewish (ASJ)

AF:

0.0620

AC:

1614

AN:

26044

East Asian (EAS)

AF:

0.166

AC:

6561

AN:

39574

South Asian (SAS)

AF:

0.0331

AC:

2841

AN:

85798

European-Finnish (FIN)

AF:

0.0462

AC:

2466

AN:

53372

Middle Eastern (MID)

AF:

0.0661

AC:

380

AN:

5750

European-Non Finnish (NFE)

AF:

0.0422

AC:

46625

AN:

1105960

Other (OTH)

AF:

0.0819

AC:

4919

AN:

60054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

2863

5726

8590

11453

14316

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.191

AC:

28964

AN:

151970

Hom.:

6492

Cov.:

AF XY:

0.186

AC XY:

13832

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.546

AC:

22571

AN:

41344

American (AMR)

AF:

0.0919

AC:

1406

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0652

AC:

226

AN:

3468

East Asian (EAS)

AF:

0.157

AC:

813

AN:

5166

South Asian (SAS)

AF:

0.0354

AC:

171

AN:

4826

European-Finnish (FIN)

AF:

0.0525

AC:

555

AN:

10572

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0423

AC:

2879

AN:

67988

Other (OTH)

AF:

0.141

AC:

297

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

810

1621

2431

3242

4052

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0669

Hom.:

860

Bravo

AF:

0.210

TwinsUK

AF:

0.0426

AC:

158

ALSPAC

AF:

0.0426

AC:

164

ESP6500AA

AF:

0.525

AC:

2309

ESP6500EA

AF:

0.0468

AC:

402

ExAC

AF:

0.0944

AC:

11466

Asia WGS

AF:

0.103

AC:

358

AN:

3478

EpiCase

AF:

0.0416

EpiControl

AF:

0.0423

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.24

(source)

DANN

Benign

0.099

DEOGEN2

Benign

0.0012

.;.;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0030

LIST_S2

Benign

0.17

T;T;T

MetaRNN

Benign

0.000012

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.90

.;N;N

PhyloP100

-0.43

PrimateAI

Benign

0.30

PROVEAN

Benign

0.85

N;N;N

REVEL

Benign

0.047

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

.;.;B

Vest4

0.073

MPC

0.16

ClinPred

0.00026

GERP RS

-1.0

Varity_R

0.063

gMVP

0.43

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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NM_001146729.2:c.247G>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over