Variant 1-15578987-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024758.5(AGMAT):c.592A>C(p.Lys198Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000583 in 1,613,940 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00060 ( 0 hom. )

Consequence

AGMAT
NM_024758.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.58

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20389763).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGMAT	NM_024758.5 linkuse as main transcript	c.592A>C	p.Lys198Gln	missense_variant	4/7	ENST00000375826.4	NP_079034.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGMAT	ENST00000375826.4 linkuse as main transcript	c.592A>C	p.Lys198Gln	missense_variant	4/7	1	NM_024758.5	ENSP00000364986	P1
DNAJC16	ENST00000483270.1 linkuse as main transcript	n.2726+3515T>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.000414

AC:

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000765

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000386

AC:

AN:

251316

Hom.:

AF XY:

0.000397

AC XY:

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00159

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000739

Gnomad NFE exome

AF:

0.000519

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000601

AC:

878

AN:

1461874

Hom.:

Cov.:

AF XY:

0.000557

AC XY:

405

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00149

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000712

Gnomad4 NFE exome

AF:

0.000699

Gnomad4 OTH exome

AF:

0.000364

GnomAD4 genome

AF:

0.000414

AC:

AN:

152066

Hom.:

Cov.:

AF XY:

0.000310

AC XY:

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.000765

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000629

Hom.:

Bravo

AF:

0.000344

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000255

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000415

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 01, 2022

The c.592A>C (p.K198Q) alteration is located in exon 4 (coding exon 4) of the AGMAT gene. This alteration results from a A to C substitution at nucleotide position 592, causing the lysine (K) at amino acid position 198 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.49

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.67

M_CAP

Benign

0.074

MetaRNN

Benign

0.20

MetaSVM

Uncertain

0.028

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-2.9

REVEL

Uncertain

0.42

Sift

Uncertain

0.020

Sift4G

Uncertain

0.043

Polyphen

0.038

Vest4

0.59

MVP

0.84

MPC

0.44

ClinPred

0.18

GERP RS

5.9

Varity_R

0.72

gMVP

0.75

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over