7-15201316-A-G

Variant names:

• chr7-15201316-A-G
• rs1389508255
• NM_001004320.2:c.1307T>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001004320.2(AGMO):​c.1307T>C​(p.Met436Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,716 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: AGMO NM_001004320.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.48

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]

ACMG classification

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=0.108013034).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGMO	NM_001004320.2	c.1307T>C	p.Met436Thr	missense_variant	Exon 13 of 13	ENST00000342526.8	NP_001004320.1
AGMO	XM_011515402.4	c.1264-41853T>C		intron_variant	Intron 12 of 12		XP_011513704.1
AGMO	XM_017012204.2	c.1264-42949T>C		intron_variant	Intron 12 of 12		XP_016867693.1
AGMO	XR_001744759.1	n.1434-42949T>C		intron_variant	Intron 12 of 16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGMO	ENST00000342526.8	c.1307T>C	p.Met436Thr	missense_variant	Exon 13 of 13	1	NM_001004320.2	ENSP00000341662.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460716 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 726636

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 16, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1307T>C (p.M436T) alteration is located in exon 13 (coding exon 13) of the AGMO gene. This alteration results from a T to C substitution at nucleotide position 1307, causing the methionine (M) at amino acid position 436 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	23
DANN	Benign	0.95
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.094
Eigen_PC	Benign	0.083
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.046
Sift	Uncertain	0.025	D
Sift4G	Benign	0.087	T
Polyphen		0.039	B
Vest4		0.33
MutPred		0.46		Gain of sheet (P = 0.0477);
MVP		0.14
MPC		0.0012
ClinPred		0.60	D
GERP RS		5.2
Varity_R		0.23
gMVP		0.56

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

Other links and lift over

dbSNP: rs1389508255; hg19: chr7-15240941;