rs12531027

Positions:

• chr7-15296311-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

LOC124901592 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGMO	NM_001004320.2	c.1263+69203A>G		intron_variant		ENST00000342526.8
LOC124901592	XR_007060218.1	n.62-14557T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGMO	ENST00000342526.8	c.1263+69203A>G		intron_variant		1	NM_001004320.2	P1

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

Gnomad4 AFR AF: 0.0703

Gnomad4 AMR AF: 0.0639

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.0857

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.0977

Alfa AF: 0.107 Hom.: 720

Bravo AF: 0.0877

Asia WGS AF: 0.0490 AC: 171 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.8
DANN	Benign	0.77

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: rs12531027; hg19: chr7-15335936;