Variant 3-119628778-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_015900.4(PLA1A):c.1199A>T(p.Lys400Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,613,972 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

PLA1A
NM_015900.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.59

Variant links:

Genes affected

PLA1A (HGNC:17661): (phospholipase A1 member A) The protein encoded by this gene is a phospholipase that hydrolyzes fatty acids at the sn-1 position of phosphatidylserine and 1-acyl-2-lysophosphatidylserine. This secreted protein hydrolyzes phosphatidylserine in liposomes. Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2011]

PLA1A links:

PLA1A (HGNC:):

PLA1A links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.749

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA1A	NM_015900.4 linkuse as main transcript	c.1199A>T	p.Lys400Met	missense_variant	10/11	ENST00000273371.9	NP_056984.1	Q53H76-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PLA1A	ENST00000273371.9 linkuse as main transcript	c.1199A>T	p.Lys400Met	missense_variant	10/11	1	NM_015900.4	ENSP00000273371.4	Q53H76-1
PLA1A	ENST00000494440.5 linkuse as main transcript	c.1151A>T	p.Lys384Met	missense_variant	10/11	1		ENSP00000418793.1	G5E9W0
PLA1A	ENST00000495992.5 linkuse as main transcript	c.1151A>T	p.Lys384Met	missense_variant	10/11	1		ENSP00000417326.1	Q53H76-3
PLA1A	ENST00000488919.5 linkuse as main transcript	c.680A>T	p.Lys227Met	missense_variant	9/10	2		ENSP00000420625.1	Q53H76-4

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152198

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:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251466

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1461774

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000162

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000301

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000247

AC:

Asia WGS

AF:

0.00202

AC:

AN:

3478

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 28, 2024

The c.1199A>T (p.K400M) alteration is located in exon 10 (coding exon 10) of the PLA1A gene. This alteration results from a A to T substitution at nucleotide position 1199, causing the lysine (K) at amino acid position 400 to be replaced by a methionine (M). 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

0.17

BayesDel_addAF

Uncertain

0.055

BayesDel_noAF

Uncertain

0.010

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.070

T;.;.;.

Eigen

Benign

0.10

Eigen_PC

Benign

0.076

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.78

T;T;T;T

M_CAP

Uncertain

0.14

MetaRNN

Pathogenic

0.75

D;D;D;D

MetaSVM

Uncertain

-0.028

MutationAssessor

Uncertain

2.7

M;.;.;.

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.43

N;N;N;N

REVEL

Uncertain

0.41

Sift

Uncertain

0.010

D;D;D;D

Sift4G

Uncertain

0.039

D;D;D;D

Polyphen

0.93

P;.;D;.

Vest4

0.60

MutPred

0.49

Loss of methylation at K400 (P = 0.0126);.;.;.;

MVP

0.90

MPC

0.30

ClinPred

0.63

GERP RS

4.2

Varity_R

0.085

gMVP

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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