Variant 7-15365563-C-T 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_001004320.2(AGMO):c.1214G>A(p.Arg405Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000376 in 1,612,680 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00036 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00038 ( 6 hom. )

Consequence

AGMO
NM_001004320.2 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0980

Variant links:

Genes affected

AGMO (HGNC:33784): (alkylglycerol monooxygenase) The protein encoded by this gene is a tetrahydrobiopterin- and iron-dependent enzyme that cleaves the ether bond of alkylglycerols. Sequence comparisons distinguish this protein as forming a third, distinct class of tetrahydrobiopterin-dependent enzymes. Variations in this gene have been associated with decreased glucose-stimulated insulin response, type 2 diabetes, and susceptibility to intracranial aneurysms. [provided by RefSeq, Aug 2012]

AGMO 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=0.0037632883).

BP6

Variant 7-15365563-C-T is Benign according to our data. Variant chr7-15365563-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1336027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGMO	NM_001004320.2 linkuse as main transcript	c.1214G>A	p.Arg405Gln	missense_variant	12/13	ENST00000342526.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
AGMO	ENST00000342526.8 linkuse as main transcript	c.1214G>A	p.Arg405Gln	missense_variant	12/13	1	NM_001004320.2	P1
AGMO	ENST00000407277.6 linkuse as main transcript	c.107G>A	p.Arg36Gln	missense_variant	2/3	3
AGMO	ENST00000418075.1 linkuse as main transcript	c.140G>A	p.Arg47Gln	missense_variant	2/3	3

Frequencies

GnomAD3 genomes

AF:

0.000356

AC:

AN:

151780

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000653

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00519

Gnomad FIN

AF:

0.0000946

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000793

AC:

199

AN:

250940

Hom.:

AF XY:

0.000951

AC XY:

129

AN XY:

135610

show subpopulations

Gnomad AFR exome

AF:

0.000432

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00494

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000264

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000378

AC:

552

AN:

1460782

Hom.:

Cov.:

AF XY:

0.000504

AC XY:

366

AN XY:

726670

show subpopulations

Gnomad4 AFR exome

AF:

0.000359

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00479

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.0000702

Gnomad4 OTH exome

AF:

0.000547

GnomAD4 genome

AF:

0.000356

AC:

AN:

151898

Hom.:

Cov.:

AF XY:

0.000485

AC XY:

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.000651

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00520

Gnomad4 FIN

AF:

0.0000946

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000134

Hom.:

Bravo

AF:

0.000204

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000955

AC:

116

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Dec 07, 2017

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.014

T;.

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.85

T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.0038

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

M;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.44

N;N

REVEL

Benign

0.059

Sift

Benign

0.15

T;D

Sift4G

Benign

0.58

T;D

Polyphen

0.26

B;.

Vest4

0.46

MVP

0.19

MPC

0.0013

ClinPred

0.0095

GERP RS

2.0

Varity_R

0.056

gMVP

0.52

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