Variant 11-63491031-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001146729.2(PLAAT5):c.4G>A(p.Gly2Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000152 in 1,445,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000098 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000054 ( 0 hom. )

Consequence

PLAAT5
NM_001146729.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.72

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33318824).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLAAT5	NM_001146729.2 linkuse as main transcript	c.4G>A	p.Gly2Ser	missense_variant	1/6	ENST00000540857.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLAAT5	ENST00000540857.6 linkuse as main transcript	c.4G>A	p.Gly2Ser	missense_variant	1/6	1	NM_001146729.2	A2	Q96KN8-3
PLAAT5	ENST00000301790.4 linkuse as main transcript	c.4G>A	p.Gly2Ser	missense_variant	1/6	1		P2	Q96KN8-1
PLAAT5	ENST00000539221.5 linkuse as main transcript	c.4G>A	p.Gly2Ser	missense_variant	1/6	1			Q96KN8-2

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.00000541

AC:

AN:

1293604

Hom.:

Cov.:

AF XY:

0.00000475

AC XY:

AN XY:

631398

show subpopulations

Gnomad4 AFR exome

AF:

0.000156

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:

0.00000194

Gnomad4 OTH exome

AF:

0.0000189

GnomAD4 genome

AF:

0.0000985

AC:

AN:

152308

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000869

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

Mar 02, 2023

The c.4G>A (p.G2S) 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 4, causing the glycine (G) at amino acid position 2 to be replaced by a serine (S). 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

Uncertain

0.38

BayesDel_addAF

Benign

-0.049

BayesDel_noAF

Benign

-0.31

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Benign

0.17

Eigen_PC

Benign

0.074

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.55

T;T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.33

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.0

L;L;L

MutationTaster

Benign

0.74

N;N;N

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.70

N;N;N

REVEL

Benign

0.16

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

.;.;D

Vest4

0.35

MutPred

0.16

Gain of phosphorylation at G2 (P = 0.0123);Gain of phosphorylation at G2 (P = 0.0123);Gain of phosphorylation at G2 (P = 0.0123);

MVP

0.42

MPC

0.58

ClinPred

0.88

GERP RS

2.6

Varity_R

0.16

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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