dbSNP rs80328842: AGMO:p.Leu395Phe (chr7-15365594-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001004320.2(AGMO):c.1183C>T(p.Leu395Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

AGMO
NM_001004320.2 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.111356676).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGMO	NM_001004320.2 link	c.1183C>T	p.Leu395Phe	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>T	p.Leu395Phe	missense_variant	Exon 12 of 13	1	NM_001004320.2	ENSP00000341662.3	Q6ZNB7
AGMO	ENST00000407277.6 link	c.73C>T	p.Leu25Phe	missense_variant	Exon 2 of 3	3		ENSP00000385742.2	H0Y3V1
AGMO	ENST00000418075.1 link	c.109C>T	p.Leu37Phe	missense_variant	Exon 2 of 3	3		ENSP00000394412.1	H7C0E0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000798

AC:

AN:

250754

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135488

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:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1460582

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726578

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:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.56

CADD

Benign

6.3

DANN

Benign

0.94

DEOGEN2

Benign

0.017

T;.

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.63

T;T

M_CAP

Benign

0.0038

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.54

N;.

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.076

Sift

Benign

0.57

T;T

Sift4G

Benign

0.95

T;T

Polyphen

0.0

B;.

Vest4

0.14

MutPred

0.31

Loss of stability (P = 0.3026);.;

MVP

0.10

MPC

0.0013

ClinPred

0.083

GERP RS

-0.26

Varity_R

0.035

gMVP

0.43

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over