Genetic Variant AGMO:p.Leu395Val (chr7-15365594-G-C) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001004320.2(AGMO):c.1183C>G(p.Leu395Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000446 in 1,612,550 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00029 ( 2 hom. )

Consequence

AGMO
NM_001004320.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.144

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010758042).

BP6

Variant 7-15365594-G-C is Benign according to our data. Variant chr7-15365594-G-C is described in ClinVar as [Benign]. Clinvar id is 3038022.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGMO	NM_001004320.2 link	c.1183C>G	p.Leu395Val	missense_variant	Exon 12 of 13	ENST00000342526.8	NP_001004320.1	Q6ZNB7X5D773

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
AGMO	ENST00000342526.8 link	c.1183C>G	p.Leu395Val	missense_variant	Exon 12 of 13	1	NM_001004320.2	ENSP00000341662.3	Q6ZNB7
AGMO	ENST00000407277.6 link	c.73C>G	p.Leu25Val	missense_variant	Exon 2 of 3	3		ENSP00000385742.2	H0Y3V1
AGMO	ENST00000418075.1 link	c.109C>G	p.Leu37Val	missense_variant	Exon 2 of 3	3		ENSP00000394412.1	H7C0E0

Frequencies

GnomAD3 genomes

AF:

0.00197

AC:

299

AN:

151854

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00667

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00112

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:

0.0000589

Gnomad OTH

AF:

0.000961

GnomAD3 exomes

AF:

0.000698

AC:

175

AN:

250754

Hom.:

AF XY:

0.000502

AC XY:

AN XY:

135488

show subpopulations

Gnomad AFR exome

AF:

0.00691

Gnomad AMR exome

AF:

0.00122

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000882

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.000288

AC:

420

AN:

1460578

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

166

AN XY:

726574

show subpopulations

Gnomad4 AFR exome

AF:

0.00919

Gnomad4 AMR exome

AF:

0.00132

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000225

Gnomad4 OTH exome

AF:

0.000398

GnomAD4 genome

AF:

0.00197

AC:

300

AN:

151972

Hom.:

Cov.:

AF XY:

0.00214

AC XY:

159

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.00668

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000589

Gnomad4 OTH

AF:

0.000951

Alfa

AF:

0.000625

Hom.:

Bravo

AF:

0.00234

ESP6500AA

AF:

0.00567

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000898

AC:

109

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000594

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

AGMO-related disorder

Benign:1

May 03, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.56

CADD

Benign

4.4

DANN

Uncertain

0.97

DEOGEN2

Benign

0.0084

T;.

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.63

T;T

M_CAP

Benign

0.0055

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.93

L;.

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.060

N;N

REVEL

Benign

0.075

Sift

Benign

0.69

T;T

Sift4G

Benign

0.79

T;T

Polyphen

0.0020

B;.

Vest4

0.16

MVP

0.15

MPC

0.0014

ClinPred

0.010

GERP RS

-0.26

Varity_R

0.037

gMVP

0.38

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