Variant 1-15578893-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_024758.5(AGMAT):c.686C>T(p.Thr229Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000864 in 1,614,134 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0042 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00052 ( 4 hom. )

Consequence

AGMAT
NM_024758.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.256

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 Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030586421).

BP6

Variant 1-15578893-G-A is Benign according to our data. Variant chr1-15578893-G-A is described in ClinVar as [Benign]. Clinvar id is 767655.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGMAT	NM_024758.5 linkuse as main transcript	c.686C>T	p.Thr229Met	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.686C>T	p.Thr229Met	missense_variant	4/7	1	NM_024758.5	ENSP00000364986	P1
DNAJC16	ENST00000483270.1 linkuse as main transcript	n.2726+3421G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.00414

AC:

630

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0140

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00109

AC:

275

AN:

251220

Hom.:

AF XY:

0.000766

AC XY:

104

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.0140

Gnomad AMR exome

AF:

0.000492

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000220

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000520

AC:

760

AN:

1461884

Hom.:

Cov.:

AF XY:

0.000485

AC XY:

353

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0137

Gnomad4 AMR exome

AF:

0.000425

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000162

Gnomad4 OTH exome

AF:

0.00151

GnomAD4 genome

AF:

0.00416

AC:

634

AN:

152250

Hom.:

Cov.:

AF XY:

0.00388

AC XY:

289

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0140

Gnomad4 AMR

AF:

0.00177

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00851

Hom.:

817

Bravo

AF:

0.00461

ESP6500AA

AF:

0.0109

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00125

AC:

152

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 30, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.52

CADD

Benign

0.077

DANN

Benign

0.93

DEOGEN2

Benign

0.12

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.17

MetaRNN

Benign

0.0031

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.72

MutationTaster

Benign

1.0

PrimateAI

Benign

0.20

PROVEAN

Benign

0.90

REVEL

Benign

0.18

Sift

Benign

0.098

Sift4G

Benign

0.063

Polyphen

0.0010

Vest4

0.27

MVP

0.33

MPC

0.32

ClinPred

0.011

GERP RS

-12

Varity_R

0.015

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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