3-119608937-A-G

Position:

• chr3-119608937-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_015900.4(PLA1A):​c.443A>G​(p.Asn148Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLA1A NM_015900.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.103

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08938393).
• BP6: Variant 3-119608937-A-G is Benign according to our data. Variant chr3-119608937-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3214045.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA1A	NM_015900.4	c.443A>G	p.Asn148Ser	missense_variant	3/11	ENST00000273371.9	NP_056984.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLA1A	ENST00000273371.9	c.443A>G	p.Asn148Ser	missense_variant	3/11	1	NM_015900.4	ENSP00000273371.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 20, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.16
DANN	Benign	0.28
DEOGEN2	Benign	0.25	T;.;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0071	N
LIST_S2	Benign	0.71	T;T;T
M_CAP	Benign	0.084	D
MetaRNN	Benign	0.089	T;T;T
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	0.81	L;.;.
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.0	N;N;N
REVEL	Benign	0.25
Sift	Benign	0.37	T;T;T
Sift4G	Benign	0.60	T;T;T
Polyphen		0.0010	B;.;.
Vest4		0.038
MutPred		0.48		Gain of ubiquitination at K149 (P = 0.0751);.;.;
MVP		0.44
MPC		0.038
ClinPred		0.029	T
GERP RS		-4.8
Varity_R		0.029
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs2082730215; hg19: chr3-119327784;