Genetic Variant PLA1A:p.Thr112Arg (chr3-119608829-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015900.4(PLA1A):c.335C>G(p.Thr112Arg) 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 1,461,276 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T112K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PLA1A
NM_015900.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.462

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10645938).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015900.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLA1A	NM_015900.4	MANE Select	c.335C>G	p.Thr112Arg	missense	Exon 3 of 11	NP_056984.1	Q53H76-1
PLA1A	NM_001206960.2		c.335C>G	p.Thr112Arg	missense	Exon 3 of 11	NP_001193889.1	Q53H76-3
PLA1A	NM_001293225.2		c.287C>G	p.Thr96Arg	missense	Exon 3 of 11	NP_001280154.1	G5E9W0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLA1A	ENST00000273371.9	TSL:1 MANE Select	c.335C>G	p.Thr112Arg	missense	Exon 3 of 11	ENSP00000273371.4	Q53H76-1
PLA1A	ENST00000494440.5	TSL:1	c.287C>G	p.Thr96Arg	missense	Exon 3 of 11	ENSP00000418793.1	G5E9W0
PLA1A	ENST00000495992.5	TSL:1	c.335C>G	p.Thr112Arg	missense	Exon 3 of 11	ENSP00000417326.1	Q53H76-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461276

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726992

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111474

Other (OTH)

AF:

0.00

AC:

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.036

BayesDel_noAF

Benign

-0.29

CADD

Benign

3.7

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.16

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.40

M_CAP

Uncertain

0.091

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.57

MutationAssessor

Benign

0.49

PhyloP100

0.46

PrimateAI

Benign

0.33

PROVEAN

Benign

0.38

REVEL

Benign

0.16

Sift

Benign

0.17

Sift4G

Benign

0.24

Polyphen

0.044

Vest4

0.18

MutPred

0.48

Gain of solvent accessibility (P = 0.024)

MVP

0.69

MPC

0.051

ClinPred

0.16

GERP RS

2.2

PromoterAI

-0.0030

Neutral

(source)

Varity_R

0.082

gMVP

0.47

Mutation Taster

=98/2

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over