Variant 11-63490963-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001146729.2(PLAAT5):c.72A>C(p.Lys24Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000064 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PLAAT5
NM_001146729.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.383

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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.026563168).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLAAT5	NM_001146729.2 linkuse as main transcript	c.72A>C	p.Lys24Asn	missense_variant	1/6	ENST00000540857.6	NP_001140201.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLAAT5	ENST00000540857.6 linkuse as main transcript	c.72A>C	p.Lys24Asn	missense_variant	1/6	1	NM_001146729.2	ENSP00000444809	A2	Q96KN8-3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

150168

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000731

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000660

Gnomad ASJ

AF:

0.00117

Gnomad EAS

AF:

0.000198

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00333

Gnomad NFE

AF:

0.000686

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000636

AC:

AN:

1430402

Hom.:

Cov.:

AF XY:

0.0000761

AC XY:

AN XY:

709620

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000248

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00157

Gnomad4 NFE exome

AF:

0.00000911

Gnomad4 OTH exome

AF:

0.0000338

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000373

AC:

AN:

150278

Hom.:

Cov.:

AF XY:

0.000450

AC XY:

AN XY:

73314

show subpopulations

Gnomad4 AFR

AF:

0.0000729

Gnomad4 AMR

AF:

0.0000659

Gnomad4 ASJ

AF:

0.00117

Gnomad4 EAS

AF:

0.000198

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000686

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.000282

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

Mar 24, 2023

The c.72A>C (p.K24N) alteration is located in exon 1 (coding exon 1) of the HRASLS5 gene. This alteration results from a A to C substitution at nucleotide position 72, causing the lysine (K) at amino acid position 24 to be replaced by an asparagine (N). 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

0.29

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.47

DEOGEN2

Benign

0.0041

.;.;T

Eigen

Benign

-0.94

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.063

LIST_S2

Benign

0.43

T;T;T

M_CAP

Benign

0.0071

MetaRNN

Benign

0.027

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

L;L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.29

N;N;N

REVEL

Benign

0.023

Sift

Uncertain

0.0040

D;D;D

Sift4G

Uncertain

0.0090

D;D;D

Polyphen

0.42

.;.;B

Vest4

0.12

MutPred

0.20

Loss of methylation at K24 (P = 0.0011);Loss of methylation at K24 (P = 0.0011);Loss of methylation at K24 (P = 0.0011);

MVP

0.25

MPC

0.20

ClinPred

0.031

GERP RS

-0.15

Varity_R

0.071

gMVP

0.19

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