dbSNP rs11580170: AGMAT:p.Arg140Gln (chr1-15583249-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024758.5(AGMAT):c.419G>A(p.Arg140Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 1,613,544 control chromosomes in the GnomAD database, including 56,087 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.32 ( 9264 hom., cov: 31)

Exomes 𝑓: 0.25 ( 46823 hom. )

Consequence

AGMAT
NM_024758.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.558

Publications

42 publications found

Variant links:

Genes affected

AGMAT (HGNC:18407): (agmatinase (putative)) Predicted to enable agmatinase activity. Predicted to be involved in putrescine biosynthetic process from arginine, using agmatinase. Predicted to be located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

AGMAT links:

DNAJC16 (HGNC:29157): (DnaJ heat shock protein family (Hsp40) member C16) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

DNAJC16 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.970299E-4).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGMAT	NM_024758.5 link	c.419G>A	p.Arg140Gln	missense_variant	Exon 2 of 7	ENST00000375826.4	NP_079034.3	Q9BSE5A0A024QZ74

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGMAT	ENST00000375826.4 link	c.419G>A	p.Arg140Gln	missense_variant	Exon 2 of 7	1	NM_024758.5	ENSP00000364986.3		Q9BSE5
DNAJC16	ENST00000483270.1 link	n.2726+7777C>T		intron_variant	Intron 13 of 13	1

Frequencies

GnomAD3 genomes

AF:

0.321

AC:

48690

AN:

151784

Hom.:

9237

Cov.:

show subpopulations

Gnomad AFR

AF:

0.524

Gnomad AMI

AF:

0.317

Gnomad AMR

AF:

0.216

Gnomad ASJ

AF:

0.271

Gnomad EAS

AF:

0.0653

Gnomad SAS

AF:

0.190

Gnomad FIN

AF:

0.303

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.255

Gnomad OTH

AF:

0.303

GnomAD2 exomes

AF:

0.242

AC:

60937

AN:

251288

AF XY:

0.241

show subpopulations

Gnomad AFR exome

AF:

0.517

Gnomad AMR exome

AF:

0.143

Gnomad ASJ exome

AF:

0.276

Gnomad EAS exome

AF:

0.0657

Gnomad FIN exome

AF:

0.299

Gnomad NFE exome

AF:

0.253

Gnomad OTH exome

AF:

0.253

GnomAD4 exome

AF:

0.246

AC:

359591

AN:

1461642

Hom.:

46823

Cov.:

AF XY:

0.245

AC XY:

178308

AN XY:

727130

show subpopulations

African (AFR)

AF:

0.527

AC:

17636

AN:

33472

American (AMR)

AF:

0.151

AC:

6729

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.280

AC:

7306

AN:

26136

East Asian (EAS)

AF:

0.0775

AC:

3075

AN:

39698

South Asian (SAS)

AF:

0.217

AC:

18675

AN:

86250

European-Finnish (FIN)

AF:

0.299

AC:

15963

AN:

53390

Middle Eastern (MID)

AF:

0.309

AC:

1772

AN:

5742

European-Non Finnish (NFE)

AF:

0.246

AC:

272985

AN:

1111860

Other (OTH)

AF:

0.256

AC:

15450

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

14837

29674

44512

59349

74186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9130

18260

27390

36520

45650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.321

AC:

48755

AN:

151902

Hom.:

9264

Cov.:

AF XY:

0.318

AC XY:

23577

AN XY:

74224

show subpopulations

African (AFR)

AF:

0.525

AC:

21711

AN:

41380

American (AMR)

AF:

0.216

AC:

3297

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.271

AC:

941

AN:

3470

East Asian (EAS)

AF:

0.0655

AC:

338

AN:

5164

South Asian (SAS)

AF:

0.188

AC:

906

AN:

4812

European-Finnish (FIN)

AF:

0.303

AC:

3201

AN:

10552

Middle Eastern (MID)

AF:

0.296

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.255

AC:

17356

AN:

67958

Other (OTH)

AF:

0.300

AC:

631

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1546

3091

4637

6182

7728

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

452

904

1356

1808

2260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.271

Hom.:

20881

Bravo

AF:

0.323

ESP6500AA

AF:

0.525

AC:

2311

ESP6500EA

AF:

0.248

AC:

2130

ExAC

AF:

0.251

AC:

30439

Asia WGS

AF:

0.171

AC:

594

AN:

3478

EpiCase

AF:

0.253

EpiControl

AF:

0.247

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.13

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.19

LIST_S2

Uncertain

0.95

MetaRNN

Benign

0.00060

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.33

PhyloP100

0.56

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.92

REVEL

Benign

0.076

Sift

Benign

0.62

Sift4G

Benign

0.62

Polyphen

0.016

Vest4

0.038

MPC

0.35

ClinPred

0.00083

GERP RS

1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.092

gMVP

0.64

Mutation Taster

=65/35

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over