Variant chr3-119628844-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_015900.4(PLA1A):c.1265C>T(p.Ala422Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,660 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: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PLA1A
NM_015900.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.26

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3802809).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA1A	NM_015900.4 linkuse as main transcript	c.1265C>T	p.Ala422Val	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.1265C>T	p.Ala422Val	missense_variant	10/11	1	NM_015900.4	ENSP00000273371.4	Q53H76-1
PLA1A	ENST00000494440.5 linkuse as main transcript	c.1217C>T	p.Ala406Val	missense_variant	10/11	1		ENSP00000418793.1	G5E9W0
PLA1A	ENST00000495992.5 linkuse as main transcript	c.1217C>T	p.Ala406Val	missense_variant	10/11	1		ENSP00000417326.1	Q53H76-3
PLA1A	ENST00000488919.5 linkuse as main transcript	c.746C>T	p.Ala249Val	missense_variant	9/10	2		ENSP00000420625.1	Q53H76-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461660

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727140

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 18, 2021

The c.1265C>T (p.A422V) alteration is located in exon 10 (coding exon 10) of the PLA1A gene. This alteration results from a C to T substitution at nucleotide position 1265, causing the alanine (A) at amino acid position 422 to be replaced by a valine (V). 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

0.12

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.079

T;.;.;.

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.099

LIST_S2

Benign

0.84

T;T;T;T

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.38

T;T;T;T

MetaSVM

Benign

-0.34

MutationAssessor

Uncertain

2.5

M;.;.;.

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.79

N;N;N;N

REVEL

Uncertain

0.34

Sift

Uncertain

0.013

D;D;D;D

Sift4G

Uncertain

0.057

T;D;T;T

Polyphen

0.52

P;.;P;.

Vest4

0.53

MutPred

0.40

Gain of sheet (P = 0.0149);.;.;.;

MVP

0.80

MPC

0.066

ClinPred

0.48

GERP RS

4.3

Varity_R

0.071

gMVP

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over