Variant chr7-15365596-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001004320.2(AGMO):c.1181C>G(p.Thr394Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000135 in 1,612,506 control chromosomes in the GnomAD database, including 6 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 Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00014 ( 6 hom. )

Consequence

AGMO
NM_001004320.2 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.81

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=0.009604335).

BP6

Variant 7-15365596-G-C is Benign according to our data. Variant chr7-15365596-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3045580.Status of the report is no_assertion_criteria_provided, 0 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.1181C>G	p.Thr394Ser	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.1181C>G	p.Thr394Ser	missense_variant	12/13	1	NM_001004320.2	P1
AGMO	ENST00000407277.6 linkuse as main transcript	c.74C>G	p.Thr25Ser	missense_variant	2/3	3
AGMO	ENST00000418075.1 linkuse as main transcript	c.107C>G	p.Thr36Ser	missense_variant	2/3	3

Frequencies

GnomAD3 genomes

AF:

0.0000659

AC:

AN:

151850

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000303

AC:

AN:

250762

Hom.:

AF XY:

0.000428

AC XY:

AN XY:

135496

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00245

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000142

AC:

208

AN:

1460538

Hom.:

Cov.:

AF XY:

0.000219

AC XY:

159

AN XY:

726548

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00233

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.0000658

AC:

AN:

151968

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.000362

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

AGMO-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 10, 2022

This variant is classified as likely 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

0.12

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.012

T;.

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.11

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.64

T;T

M_CAP

Benign

0.0083

MetaRNN

Benign

0.0096

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

M;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.72

N;N

REVEL

Benign

0.056

Sift

Benign

0.061

T;T

Sift4G

Uncertain

0.024

D;D

Polyphen

0.045

B;.

Vest4

0.41

MutPred

0.44

Gain of disorder (P = 0.3566);.;

MVP

0.19

MPC

0.0016

ClinPred

0.041

GERP RS

4.9

Varity_R

0.079

gMVP

0.42

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