4-109714393-T-C

Position:

• chr4-109714393-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_030821.5(PLA2G12A):​c.554A>G​(p.Glu185Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLA2G12A NM_030821.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.55

Genes affected

PLA2G12A (HGNC:18554): (phospholipase A2 group XIIA) Secreted phospholipase A2 (sPLA2) enzymes liberate arachidonic acid from phospholipids for production of eicosanoids and exert a variety of physiologic and pathologic effects. Group XII sPLA2s, such as PLA2G12A, have relatively low specific activity and are structurally and functionally distinct from other sPLA2s (Gelb et al., 2000 [PubMed 11031251]).[supplied by OMIM, Mar 2008]

ENSG00000285330 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA2G12A	NM_030821.5	c.554A>G	p.Glu185Gly	missense_variant	4/4	ENST00000243501.10	NP_110448.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLA2G12A	ENST00000243501.10	c.554A>G	p.Glu185Gly	missense_variant	4/4	1	NM_030821.5	ENSP00000243501.5
ENSG00000285330	ENST00000645635.1	c.1880A>G	p.Glu627Gly	missense_variant	15/15			ENSP00000493607.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 04, 2024

The c.554A>G (p.E185G) alteration is located in exon 4 (coding exon 4) of the PLA2G12A gene. This alteration results from a A to G substitution at nucleotide position 554, causing the glutamic acid (E) at amino acid position 185 to be replaced by a glycine (G). 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	0.15
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T;T;.
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.017
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.68	T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.48	T;T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.6	M;.;.
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.4	D;D;.
REVEL	Benign	0.15
Sift	Uncertain	0.019	D;D;.
Sift4G	Uncertain	0.053	T;T;.
Polyphen		0.012	B;.;.
Vest4		0.061
MutPred		0.70		Loss of stability (P = 0.0053);.;.;
MVP		0.44
MPC		0.084
ClinPred		0.98	D
GERP RS		4.9
Varity_R		0.15
gMVP		0.61

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-110635549;