NM_001004320.2:c.1263+69203A>G

Variant names:

• chr7-15296311-T-C
• rs12531027
• NM_001004320.2:c.1263+69203A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001004320.2(AGMO):​c.1263+69203A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 152,158 control chromosomes in the GnomAD database, including 926 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.10 (926 hom., cov: 32)
• Consequence: AGMO NM_001004320.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.73
• Publications: 4 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

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.1263+69203A>G		intron	N/A	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.1263+69203A>G		intron	N/A	ENSP00000341662.3	Q6ZNB7
	AGMO	ENST00000859218.1		c.1251+69203A>G		intron	N/A	ENSP00000529277.1
	AGMO	ENST00000859216.1		c.1197+69203A>G		intron	N/A	ENSP00000529275.1

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15261 AN: 152040 Hom.: 926 Cov.: 32

Gnomad AFR AF: 0.0702

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.0640

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0855

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.0997

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.100 AC: 15266 AN: 152158 Hom.: 926 Cov.: 32 AF XY: 0.103 AC XY: 7671 AN XY: 74372

African (AFR) AF: 0.0703 AC: 2918 AN: 41520

American (AMR) AF: 0.0639 AC: 976 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 430 AN: 3468

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5176

South Asian (SAS) AF: 0.0857 AC: 414 AN: 4828

European-Finnish (FIN) AF: 0.206 AC: 2176 AN: 10564

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7959 AN: 68010

Other (OTH) AF: 0.0977 AC: 206 AN: 2108

Alfa AF: 0.102 Hom.: 1107

Bravo AF: 0.0877

Asia WGS AF: 0.0490 AC: 171 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.8
DANN	Benign	0.77
PhyloP100		2.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12531027; hg19: chr7-15335936;