chr3-119616047-T-C

Variant names:

• chr3-119616047-T-C
• NM_015900.4:c.700T>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_015900.4(PLA1A):​c.700T>C​(p.Tyr234His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLA1A NM_015900.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.10
• 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.922

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.700T>C	p.Tyr234His	missense	Exon 6 of 11	NP_056984.1	Q53H76-1
	PLA1A	NM_001206960.2		c.652T>C	p.Tyr218His	missense	Exon 6 of 11	NP_001193889.1	Q53H76-3
	PLA1A	NM_001293225.2		c.652T>C	p.Tyr218His	missense	Exon 6 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.700T>C	p.Tyr234His	missense	Exon 6 of 11	ENSP00000273371.4	Q53H76-1
	PLA1A	ENST00000494440.5	TSL:1	c.652T>C	p.Tyr218His	missense	Exon 6 of 11	ENSP00000418793.1	G5E9W0
	PLA1A	ENST00000495992.5	TSL:1	c.652T>C	p.Tyr218His	missense	Exon 6 of 11	ENSP00000417326.1	Q53H76-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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	Pathogenic	0.85
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.70	D
Eigen	Benign	0.022
Eigen_PC	Benign	0.12
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.92	D
MetaSVM	Uncertain	0.31	D
MutationAssessor	Pathogenic	3.0	M
PhyloP100		7.1
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-4.2	D
REVEL	Uncertain	0.63
Sift	Benign	0.046	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.021	B
Vest4		0.87
MutPred		0.80		Gain of disorder (P = 0.0154)
MVP		0.84
MPC		0.077
ClinPred		0.99	D
GERP RS		4.1
Varity_R		0.66
gMVP		0.95
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr3-119334894;