3-119606791-C-A

Variant names:

• chr3-119606791-C-A
• rs756340208
• NM_015900.4:c.91C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015900.4(PLA1A):​c.91C>A​(p.Pro31Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PLA1A NM_015900.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.614
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05325395).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA1A	NM_015900.4	MANE Select	c.91C>A	p.Pro31Thr	missense	Exon 2 of 11	NP_056984.1	Q53H76-1
	PLA1A	NM_001206960.2		c.91C>A	p.Pro31Thr	missense	Exon 2 of 11	NP_001193889.1	Q53H76-3
	PLA1A	NM_001293225.2		c.43C>A	p.Pro15Thr	missense	Exon 2 of 11	NP_001280154.1	G5E9W0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA1A	ENST00000273371.9	TSL:1 MANE Select	c.91C>A	p.Pro31Thr	missense	Exon 2 of 11	ENSP00000273371.4	Q53H76-1
	PLA1A	ENST00000494440.5	TSL:1	c.43C>A	p.Pro15Thr	missense	Exon 2 of 11	ENSP00000418793.1	G5E9W0
	PLA1A	ENST00000495992.5	TSL:1	c.91C>A	p.Pro31Thr	missense	Exon 2 of 11	ENSP00000417326.1	Q53H76-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461764 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727206

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111934

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	2.6
DANN	Benign	0.65
DEOGEN2	Benign	0.15	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	-0.21	N
PhyloP100		-0.61
PrimateAI	Benign	0.20	T
PROVEAN	Benign	0.61	N
REVEL	Benign	0.13
Sift	Benign	0.24	T
Sift4G	Benign	0.27	T
Polyphen		0.0030	B
Vest4		0.12
MutPred		0.41		Gain of phosphorylation at P31 (P = 0.0296)
MVP		0.46
MPC		0.048
ClinPred		0.063	T
GERP RS		-1.1
Varity_R		0.035
gMVP		0.26
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs756340208; hg19: chr3-119325638;