3-119613072-T-G

Variant names:

• chr3-119613072-T-G
• NM_015900.4:c.618T>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_015900.4(PLA1A):​c.618T>G​(p.Asp206Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,156 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: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PLA1A NM_015900.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0990

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.882

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA1A	NM_015900.4	c.618T>G	p.Asp206Glu	missense_variant	Exon 5 of 11	ENST00000273371.9	NP_056984.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA1A	ENST00000273371.9	c.618T>G	p.Asp206Glu	missense_variant	Exon 5 of 11	1	NM_015900.4	ENSP00000273371.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457156 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 724186

Gnomad4 AFR exome AF: 0.0000299

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 27, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.618T>G (p.D206E) alteration is located in exon 5 (coding exon 5) of the PLA1A gene. This alteration results from a T to G substitution at nucleotide position 618, causing the aspartic acid (D) at amino acid position 206 to be replaced by a glutamic acid (E). 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	Pathogenic	0.71
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.27
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.71	D;.;.;.;.
Eigen	Benign	-0.0010
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.23	N
LIST_S2	Uncertain	0.86	D;D;T;D;D
M_CAP	Uncertain	0.18	D
MetaRNN	Pathogenic	0.88	D;D;D;D;D
MetaSVM	Pathogenic	0.82	D
MutationAssessor	Pathogenic	3.2	M;.;.;.;.
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.7	D;D;D;D;D
REVEL	Pathogenic	0.76
Sift	Uncertain	0.0030	D;D;D;D;D
Sift4G	Uncertain	0.010	D;D;D;D;D
Polyphen		1.0	D;.;D;.;.
Vest4		0.88
MutPred		0.71		Gain of disorder (P = 0.1102);.;.;.;.;
MVP		0.90
MPC		0.30
ClinPred		0.99	D
GERP RS		-0.57
Varity_R		0.80
gMVP		0.87

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: chr3-119331919;