Variant 11-63490994-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_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. 14/21 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 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00029 ( 0 hom. )

Consequence

PLAAT5
NM_001146729.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.35

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLAAT5	NM_001146729.2 linkuse as main transcript	c.41G>A	p.Arg14His	missense_variant	1/6	ENST00000540857.6	NP_001140201.2	Q8NE88

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PLAAT5	ENST00000540857.6 linkuse as main transcript	c.41G>A	p.Arg14His	missense_variant	1/6	1	NM_001146729.2	ENSP00000444809.1	Q96KN8-3
PLAAT5	ENST00000301790.4 linkuse as main transcript	c.41G>A	p.Arg14His	missense_variant	1/6	1		ENSP00000301790.4	Q96KN8-1
PLAAT5	ENST00000539221.5 linkuse as main transcript	c.41G>A	p.Arg14His	missense_variant	1/6	1		ENSP00000443873.1	Q96KN8-2
PLAAT5	ENST00000394615.2 linkuse as main transcript	n.-29G>A		upstream_gene_variant		4		ENSP00000378113.2	H7BYL7

Frequencies

GnomAD3 genomes

AF:

0.0000855

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.000110

AC:

AN:

144874

Hom.:

AF XY:

0.0000893

AC XY:

AN XY:

78422

show subpopulations

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 SAS 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.:

Cov.:

AF XY:

0.000266

AC XY:

184

AN XY:

690920

show subpopulations

Gnomad4 AFR exome

AF:

0.000196

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000361

Gnomad4 OTH exome

AF:

0.000173

GnomAD4 genome

AF:

0.0000855

AC:

AN:

152122

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000209

Hom.:

Bravo

AF:

0.0000642

ExAC

AF:

0.0000766

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 19, 2024

The c.41G>A (p.R14H) alteration is located in exon 1 (coding exon 1) of the HRASLS5 gene. This alteration results from a G to A substitution at nucleotide position 41, causing the arginine (R) at amino acid position 14 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.48

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

LIST_S2

Benign

0.53

T;T;T

M_CAP

Benign

0.0041

MetaRNN

Benign

0.046

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

N;N;N

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.68

N;N;N

REVEL

Benign

0.10

Sift

Uncertain

0.0080

D;D;D

Sift4G

Benign

0.069

T;T;T

Polyphen

0.92

.;.;P

Vest4

0.041

MVP

0.23

MPC

0.15

ClinPred

0.091

GERP RS

-4.0

Varity_R

0.051

gMVP

0.22

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over