7-15218831-C-T

Variant names:

• chr7-15218831-C-T
• rs6977610
• NM_001004320.2:c.1264-17472G>A

Variant summary

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

The NM_001004320.2(AGMO):​c.1264-17472G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 151,862 control chromosomes in the GnomAD database, including 4,906 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 0.24 (4906 hom., cov: 31)
• Consequence: AGMO NM_001004320.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.84
• Publications: 2 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.359 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.1264-17472G>A		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.1264-17472G>A		intron	N/A	ENSP00000341662.3	Q6ZNB7
	AGMO	ENST00000859218.1		c.1252-17472G>A		intron	N/A	ENSP00000529277.1
	AGMO	ENST00000859216.1		c.1198-17472G>A		intron	N/A	ENSP00000529275.1

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36051 AN: 151744 Hom.: 4891 Cov.: 31

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.0327

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.238 AC: 36104 AN: 151862 Hom.: 4906 Cov.: 31 AF XY: 0.237 AC XY: 17591 AN XY: 74220

African (AFR) AF: 0.363 AC: 15045 AN: 41390

American (AMR) AF: 0.244 AC: 3713 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 733 AN: 3466

East Asian (EAS) AF: 0.0326 AC: 168 AN: 5150

South Asian (SAS) AF: 0.332 AC: 1598 AN: 4812

European-Finnish (FIN) AF: 0.121 AC: 1274 AN: 10550

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12910 AN: 67952

Other (OTH) AF: 0.208 AC: 438 AN: 2106

Alfa AF: 0.203 Hom.: 3788

Bravo AF: 0.246

Asia WGS AF: 0.220 AC: 767 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.021
DANN	Benign	0.18
PhyloP100		-2.8
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: rs6977610; hg19: chr7-15258456;