chr3-119609469-T-C

Variant names:

• chr3-119609469-T-C
• rs779843014
• NM_015900.4:c.455T>C

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.455T>C​(p.Val152Ala) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,446,642 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 19/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. V152E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PLA1A NM_015900.4 missense, splice_region
• Scores: Splicing: ADA: 0.00009496
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04
• 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=0.041374147).

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.455T>C	p.Val152Ala	missense splice_region	Exon 4 of 11	NP_056984.1	Q53H76-1
	PLA1A	NM_001206960.2		c.407T>C	p.Val136Ala	missense splice_region	Exon 4 of 11	NP_001193889.1	Q53H76-3
	PLA1A	NM_001293225.2		c.407T>C	p.Val136Ala	missense splice_region	Exon 4 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.455T>C	p.Val152Ala	missense splice_region	Exon 4 of 11	ENSP00000273371.4	Q53H76-1
	PLA1A	ENST00000494440.5	TSL:1	c.407T>C	p.Val136Ala	missense splice_region	Exon 4 of 11	ENSP00000418793.1	G5E9W0
	PLA1A	ENST00000495992.5	TSL:1	c.407T>C	p.Val136Ala	missense splice_region	Exon 4 of 11	ENSP00000417326.1	Q53H76-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1446642 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 720780

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000302 AC: 1 AN: 33152

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26024

East Asian (EAS) AF: 0.00 AC: 0 AN: 39640

South Asian (SAS) AF: 0.00 AC: 0 AN: 85916

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1098208

Other (OTH) AF: 0.00 AC: 0 AN: 59854

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	0.0030
DANN	Benign	0.51
DEOGEN2	Benign	0.15	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.068	D
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	-1.0	N
PhyloP100		-2.0
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.94	N
REVEL	Benign	0.28
Sift	Benign	1.0	T
Sift4G	Benign	0.77	T
Polyphen		0.0	B
Vest4		0.089
MutPred		0.38		Loss of stability (P = 0.0241)
MVP		0.26
MPC		0.049
ClinPred		0.031	T
GERP RS		-7.6
Varity_R		0.030
gMVP		0.32
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000095
dbscSNV1_RF	Benign	0.054
SpliceAI score (max)		0.020		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: rs779843014; hg19: chr3-119328316;