7-15558531-A-G

Variant names:

• chr7-15558531-A-G
• rs978897
• NM_001004320.2:c.257+1610T>C

Variant summary

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

The NM_001004320.2(AGMO):​c.257+1610T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 151,950 control chromosomes in the GnomAD database, including 7,434 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 0.26 (7434 hom., cov: 32)
• Consequence: AGMO NM_001004320.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.539 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGMO	NM_001004320.2	MANE Select	c.257+1610T>C		intron	N/A	NP_001004320.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGMO	ENST00000342526.8	TSL:1 MANE Select	c.257+1610T>C		intron	N/A	ENSP00000341662.3

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38699 AN: 151830 Hom.: 7412 Cov.: 32

Gnomad AFR AF: 0.545

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.176

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.255 AC: 38768 AN: 151950 Hom.: 7434 Cov.: 32 AF XY: 0.251 AC XY: 18629 AN XY: 74276

African (AFR) AF: 0.545 AC: 22596 AN: 41434

American (AMR) AF: 0.122 AC: 1854 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 502 AN: 3466

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

South Asian (SAS) AF: 0.127 AC: 613 AN: 4818

European-Finnish (FIN) AF: 0.180 AC: 1904 AN: 10578

Middle Eastern (MID) AF: 0.185 AC: 54 AN: 292

European-Non Finnish (NFE) AF: 0.157 AC: 10662 AN: 67934

Other (OTH) AF: 0.197 AC: 416 AN: 2110

Alfa AF: 0.162 Hom.: 3143

Bravo AF: 0.263

Asia WGS AF: 0.0880 AC: 302 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.11
DANN	Benign	0.49
PhyloP100		-1.6
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: rs978897; hg19: chr7-15598156;