NM_015900.4:c.1134A>G

Variant names:

• chr3-119628713-A-G
• rs41271395
• NM_015900.4:c.1134A>G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_015900.4(PLA1A):​c.1134A>G​(p.Gln378Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00981 in 1,614,028 control chromosomes in the GnomAD database, including 97 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0065 (3 hom., cov: 32)
  • Exomes 𝑓: 0.010 (94 hom.)
• Consequence: PLA1A NM_015900.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0620
• Publications: 5 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: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 3-119628713-A-G is Benign according to our data. Variant chr3-119628713-A-G is described in ClinVar as Benign. ClinVar VariationId is 790979.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.062 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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.1134A>G	p.Gln378Gln	synonymous	Exon 10 of 11	NP_056984.1	Q53H76-1
	PLA1A	NM_001206960.2		c.1086A>G	p.Gln362Gln	synonymous	Exon 10 of 11	NP_001193889.1	Q53H76-3
	PLA1A	NM_001293225.2		c.1086A>G	p.Gln362Gln	synonymous	Exon 10 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.1134A>G	p.Gln378Gln	synonymous	Exon 10 of 11	ENSP00000273371.4	Q53H76-1
	PLA1A	ENST00000494440.5	TSL:1	c.1086A>G	p.Gln362Gln	synonymous	Exon 10 of 11	ENSP00000418793.1	G5E9W0
	PLA1A	ENST00000495992.5	TSL:1	c.1086A>G	p.Gln362Gln	synonymous	Exon 10 of 11	ENSP00000417326.1	Q53H76-3

Frequencies

GnomAD3 genomes AF: 0.00646 AC: 983 AN: 152204 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00176

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00222

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00584

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0118

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00667 AC: 1676 AN: 251248 AF XY: 0.00658

Gnomad AFR exome AF: 0.00185

Gnomad AMR exome AF: 0.00335

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00490

Gnomad NFE exome AF: 0.0118

Gnomad OTH exome AF: 0.00815

GnomAD4 exome AF: 0.0102 AC: 14854 AN: 1461706 Hom.: 94 Cov.: 31 AF XY: 0.00973 AC XY: 7077 AN XY: 727162

African (AFR) AF: 0.00200 AC: 67 AN: 33480

American (AMR) AF: 0.00353 AC: 158 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000421 AC: 11 AN: 26134

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.00103 AC: 89 AN: 86250

European-Finnish (FIN) AF: 0.00592 AC: 316 AN: 53420

Middle Eastern (MID) AF: 0.00832 AC: 48 AN: 5768

European-Non Finnish (NFE) AF: 0.0123 AC: 13664 AN: 1111846

Other (OTH) AF: 0.00825 AC: 498 AN: 60386

GnomAD4 genome AF: 0.00645 AC: 983 AN: 152322 Hom.: 3 Cov.: 32 AF XY: 0.00559 AC XY: 416 AN XY: 74482

African (AFR) AF: 0.00176 AC: 73 AN: 41584

American (AMR) AF: 0.00222 AC: 34 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4826

European-Finnish (FIN) AF: 0.00584 AC: 62 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0118 AC: 806 AN: 68018

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.00906 Hom.: 2

Bravo AF: 0.00599

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00938

EpiControl AF: 0.00907

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.047
DANN	Benign	0.38
PhyloP100		-0.062
Mutation Taster		=100/0	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: rs41271395; hg19: chr3-119347560; COSMIC: COSV56332467;