Genetic Variant AGMO:p.Ser361Leu (chr7-15366215-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001004320.2(AGMO):c.1082C>T(p.Ser361Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000368 in 1,602,982 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 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

AGMO
NM_001004320.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.46

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05139488).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGMO	NM_001004320.2 link	c.1082C>T	p.Ser361Leu	missense_variant	Exon 11 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.1082C>T	p.Ser361Leu	missense_variant	Exon 11 of 13	1	NM_001004320.2	ENSP00000341662.3	Q6ZNB7
AGMO	ENST00000418075.1 link	c.8C>T	p.Ser3Leu	missense_variant	Exon 1 of 3	3		ENSP00000394412.1	H7C0E0
AGMO	ENST00000407277.6 link	c.-29C>T		upstream_gene_variant		3		ENSP00000385742.2	H0Y3V1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152026

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000965

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000970

AC:

AN:

237112

Hom.:

AF XY:

0.0000859

AC XY:

AN XY:

128102

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00105

Gnomad SAS exome

AF:

0.0000700

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000284

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000358

AC:

AN:

1450840

Hom.:

Cov.:

AF XY:

0.0000347

AC XY:

AN XY:

721362

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000775

Gnomad4 SAS exome

AF:

0.0000355

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000145

Gnomad4 OTH exome

AF:

0.0000501

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000967

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000493

Hom.:

Bravo

AF:

0.000140

ExAC

AF:

0.000116

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Jun 01, 2023

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

T;.

Eigen

Benign

0.15

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.86

D;T

M_CAP

Benign

0.0091

MetaRNN

Benign

0.051

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.5

M;.

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-3.5

D;D

REVEL

Benign

0.19

Sift

Uncertain

0.020

D;D

Sift4G

Uncertain

0.023

D;D

Polyphen

0.71

P;.

Vest4

0.71

MVP

0.33

MPC

0.0018

ClinPred

0.19

GERP RS

5.9

Varity_R

0.25

gMVP

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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