rs13231

Variant names:

• chr6-160718825-A-G
• rs13231
• NM_000301.5:c.1083A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-160718825-A-G
• chr6-160718825-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000301.5(PLG):​c.1083A>G​(p.Gln361Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 1,612,288 control chromosomes in the GnomAD database, including 57,749 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4403 hom., cov: 32)
  • Exomes 𝑓: 0.26 (53346 hom.)
• Consequence: PLG NM_000301.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -4.38
• Publications: 26 publications found

Genes affected

PLG (HGNC:9071): (plasminogen) The plasminogen protein encoded by this gene is a serine protease that circulates in blood plasma as an inactive zymogen and is converted to the active protease, plasmin, by several plasminogen activators such as tissue plasminogen activator (tPA), urokinase plasminogen activator (uPA), kallikrein, and factor XII (Hageman factor). The conversion of plasminogen to plasmin involves the cleavage of the peptide bond between Arg-561 and Val-562. Plasmin cleavage also releases the angiostatin protein which inhibits angiogenesis. Plasmin degrades many blood plasma proteins, including fibrin-containing blood clots. As a serine protease, plasmin cleaves many products in addition to fibrin such as fibronectin, thrombospondin, laminin, and von Willebrand factor. Plasmin is inactivated by proteins such as alpha-2-macroglobulin and alpha-2-antiplasmin in addition to inhibitors of the various plasminogen activators. Plasminogen also interacts with plasminogen receptors which results in the retention of plasmin on cell surfaces and in plasmin-induced cell signaling. The localization of plasminogen on cell surfaces plays a role in the degradation of extracellular matrices, cell migration, inflamation, wound healing, oncogenesis, metastasis, myogenesis, muscle regeneration, neurite outgrowth, and fibrinolysis. This protein may also play a role in acute respiratory distress syndrome (ARDS) which, in part, is caused by enhanced clot formation and the suppression of fibrinolysis. Compared to other mammals, the cluster of plasminogen-like genes to which this gene belongs has been rearranged in catarrhine primates. [provided by RefSeq, May 2020]

PLG Gene-Disease associations (from GenCC):

• hypoplasminogenemia

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• angioedema, hereditary, 4

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.09).
• BP6: Variant 6-160718825-A-G is Benign according to our data. Variant chr6-160718825-A-G is described in ClinVar as Benign. ClinVar VariationId is 1174953.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.38 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLG	NM_000301.5	c.1083A>G	p.Gln361Gln	synonymous_variant	Exon 9 of 19	ENST00000308192.14	NP_000292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLG	ENST00000308192.14	c.1083A>G	p.Gln361Gln	synonymous_variant	Exon 9 of 19	1	NM_000301.5	ENSP00000308938.9
PLG	ENST00000418964.2	c.1134A>G	p.Gln378Gln	synonymous_variant	Exon 9 of 19	4		ENSP00000389424.2
PLG	ENST00000706906.1	n.1083A>G		non_coding_transcript_exon_variant	Exon 9 of 19			ENSP00000516618.1
PLG	ENST00000297289.9	c.50-3583A>G		intron_variant	Intron 1 of 10	5		ENSP00000516619.1

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34773 AN: 151998 Hom.: 4405 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.245

GnomAD2 exomes AF: 0.213 AC: 53322 AN: 250816 AF XY: 0.215

Gnomad AFR exome AF: 0.173

Gnomad AMR exome AF: 0.124

Gnomad ASJ exome AF: 0.277

Gnomad EAS exome AF: 0.000707

Gnomad FIN exome AF: 0.259

Gnomad NFE exome AF: 0.295

Gnomad OTH exome AF: 0.232

GnomAD4 exome AF: 0.260 AC: 379801 AN: 1460172 Hom.: 53346 Cov.: 34 AF XY: 0.257 AC XY: 186556 AN XY: 726472

African (AFR) AF: 0.165 AC: 5527 AN: 33454

American (AMR) AF: 0.131 AC: 5838 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 7231 AN: 26124

East Asian (EAS) AF: 0.000529 AC: 21 AN: 39696

South Asian (SAS) AF: 0.106 AC: 9167 AN: 86234

European-Finnish (FIN) AF: 0.261 AC: 13960 AN: 53412

Middle Eastern (MID) AF: 0.256 AC: 1474 AN: 5762

European-Non Finnish (NFE) AF: 0.290 AC: 321791 AN: 1110452

Other (OTH) AF: 0.245 AC: 14792 AN: 60324

GnomAD4 genome AF: 0.229 AC: 34781 AN: 152116 Hom.: 4403 Cov.: 32 AF XY: 0.224 AC XY: 16636 AN XY: 74350

African (AFR) AF: 0.170 AC: 7066 AN: 41524

American (AMR) AF: 0.201 AC: 3070 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 1001 AN: 3470

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5184

South Asian (SAS) AF: 0.101 AC: 488 AN: 4812

European-Finnish (FIN) AF: 0.259 AC: 2735 AN: 10560

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19634 AN: 67978

Other (OTH) AF: 0.243 AC: 511 AN: 2106

Alfa AF: 0.268 Hom.: 17633

Bravo AF: 0.225

Asia WGS AF: 0.0540 AC: 192 AN: 3478

EpiCase AF: 0.295

EpiControl AF: 0.307

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:2

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.028
DANN	Benign	0.27
PhyloP100		-4.4
Mutation Taster		=100/0	polymorphism (auto)

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: rs13231; hg19: chr6-161139857; COSMIC: COSV51983661;