3-119608937-A-G

Variant names:

• chr3-119608937-A-G
• rs2082730215
• NM_015900.4:c.443A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_015900.4(PLA1A):​c.443A>G​(p.Asn148Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLA1A NM_015900.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.103
• 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=0.08938393).
• BP6: Variant 3-119608937-A-G is Benign according to our data. Variant chr3-119608937-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3214045.Status of the report is criteria_provided_single_submitter, 1 stars.

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.443A>G	p.Asn148Ser	missense	Exon 3 of 11	NP_056984.1	Q53H76-1
	PLA1A	NM_001293225.2		c.395A>G	p.Asn132Ser	missense	Exon 3 of 11	NP_001280154.1	G5E9W0
	PLA1A	NM_001206961.2		c.-77A>G		5_prime_UTR	Exon 2 of 10	NP_001193890.1	Q53H76-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA1A	ENST00000273371.9	TSL:1 MANE Select	c.443A>G	p.Asn148Ser	missense	Exon 3 of 11	ENSP00000273371.4	Q53H76-1
	PLA1A	ENST00000494440.5	TSL:1	c.395A>G	p.Asn132Ser	missense	Exon 3 of 11	ENSP00000418793.1	G5E9W0
	PLA1A	ENST00000495992.5	TSL:1	c.405+38A>G		intron	N/A	ENSP00000417326.1	Q53H76-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.071
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.16
DANN	Benign	0.28
DEOGEN2	Benign	0.25	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0071	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.084	D
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.10
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.25
Sift	Benign	0.37	T
Sift4G	Benign	0.60	T
Polyphen		0.0010	B
Vest4		0.038
MutPred		0.48		Gain of ubiquitination at K149 (P = 0.0751)
MVP		0.44
MPC		0.038
ClinPred		0.029	T
GERP RS		-4.8
PromoterAI		-0.015	Neutral
Varity_R		0.029
gMVP		0.31
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2082730215; hg19: chr3-119327784;