NM_001004320.2:c.1147C>G

Variant names:

• chr7-15366150-G-C
• rs1782970276
• NM_001004320.2:c.1147C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001004320.2(AGMO):​c.1147C>G​(p.Leu383Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,454,578 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: AGMO NM_001004320.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.122
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• autism spectrum disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000309517 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19218993).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004320.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGMO	NM_001004320.2	MANE Select	c.1147C>G	p.Leu383Val	missense	Exon 11 of 13	NP_001004320.1	X5D773

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGMO	ENST00000342526.8	TSL:1 MANE Select	c.1147C>G	p.Leu383Val	missense	Exon 11 of 13	ENSP00000341662.3	Q6ZNB7
	AGMO	ENST00000859218.1		c.1135C>G	p.Leu379Val	missense	Exon 11 of 13	ENSP00000529277.1
	AGMO	ENST00000859216.1		c.1081C>G	p.Leu361Val	missense	Exon 10 of 12	ENSP00000529275.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1454578 Hom.: 0 Cov.: 30 AF XY: 0.00000277 AC XY: 2 AN XY: 723282

African (AFR) AF: 0.00 AC: 0 AN: 33070

American (AMR) AF: 0.00 AC: 0 AN: 44344

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26026

East Asian (EAS) AF: 0.00 AC: 0 AN: 39216

South Asian (SAS) AF: 0.00 AC: 0 AN: 85036

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53202

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000271 AC: 3 AN: 1107876

Other (OTH) AF: 0.00 AC: 0 AN: 60046

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.042	T
Eigen	Benign	0.063
Eigen_PC	Benign	0.071
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.12
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.099
Sift	Benign	0.12	T
Sift4G	Benign	0.28	T
Polyphen		0.0030	B
Vest4		0.32
MutPred		0.32		Gain of methylation at K388 (P = 0.0894)
MVP		0.25
MPC		0.0014
ClinPred		0.094	T
GERP RS		1.8
PromoterAI		-0.0083	Neutral
Varity_R		0.065
gMVP		0.49
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1782970276; hg19: chr7-15405775;