rs10502149

chr11-111836663-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024740.2(ALG9):c.1473-369A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 320,612 control chromosomes in the GnomAD database, including 18,707 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 0.29 (7473 hom., cov: 33)
  • Exomes 𝑓: 0.36 (11234 hom.)
• Consequence: ALG9 NM_024740.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40

Genes affected

ALG9 (HGNC:15672): (ALG9 alpha-1,2-mannosyltransferase) This gene encodes an alpha-1,2-mannosyltransferase enzyme that functions in lipid-linked oligosaccharide assembly. Mutations in this gene result in congenital disorder of glycosylation type Il. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALG9	NM_024740.2	c.1473-369A>G		intron_variant		ENST00000616540.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALG9	ENST00000616540.5	c.1473-369A>G		intron_variant		1	NM_024740.2

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44778 AN: 152052 Hom.: 7467 Cov.: 33

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.279

GnomAD4 exome AF: 0.359 AC: 60406 AN: 168442 Hom.: 11234 Cov.: 0 AF XY: 0.364 AC XY: 33325 AN XY: 91630

Gnomad4 AFR exome AF: 0.142

Gnomad4 AMR exome AF: 0.369

Gnomad4 ASJ exome AF: 0.268

Gnomad4 EAS exome AF: 0.593

Gnomad4 SAS exome AF: 0.397

Gnomad4 FIN exome AF: 0.377

Gnomad4 NFE exome AF: 0.341

Gnomad4 OTH exome AF: 0.350

GnomAD4 genome AF: 0.294 AC: 44800 AN: 152170 Hom.: 7473 Cov.: 33 AF XY: 0.302 AC XY: 22476 AN XY: 74392

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.313

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.586

Gnomad4 SAS AF: 0.393

Gnomad4 FIN AF: 0.379

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.282

Alfa AF: 0.323 Hom.: 6048

Bravo AF: 0.285

Asia WGS AF: 0.430 AC: 1495 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.34
Dann	Benign	0.71

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: rs10502149; hg19: chr11-111707386;