11-111783917-GT-G

Position:

• chr11-111783917-GT-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_024740.2(ALG9):​c.*2479del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0273 in 116,202 control chromosomes in the GnomAD database, including 113 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (113 hom., cov: 29)
  • Failed GnomAD Quality Control
• Consequence: ALG9 NM_024740.2 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.70

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALG9	NM_024740.2	c.*2479del		3_prime_UTR_variant	15/15	ENST00000616540.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALG9	ENST00000616540.5	c.*2479del		3_prime_UTR_variant	15/15	1	NM_024740.2
ALG9	ENST00000532425.6	c.*2139del		3_prime_UTR_variant	6/6	3

Frequencies

GnomAD3 genomes AF: 0.0272 AC: 3161 AN: 116140 Hom.: 113 Cov.: 29

Gnomad AFR AF: 0.0830

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0120

Gnomad ASJ AF: 0.000744

Gnomad EAS AF: 0.00784

Gnomad SAS AF: 0.0611

Gnomad FIN AF: 0.000936

Gnomad MID AF: 0.0214

Gnomad NFE AF: 0.00184

Gnomad OTH AF: 0.0216

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0273 AC: 3171 AN: 116202 Hom.: 113 Cov.: 29 AF XY: 0.0289 AC XY: 1603 AN XY: 55528

Gnomad4 AFR AF: 0.0831

Gnomad4 AMR AF: 0.0120

Gnomad4 ASJ AF: 0.000744

Gnomad4 EAS AF: 0.00786

Gnomad4 SAS AF: 0.0607

Gnomad4 FIN AF: 0.000936

Gnomad4 NFE AF: 0.00184

Gnomad4 OTH AF: 0.0240

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital disorder of glycosylation Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs376955296; hg19: chr11-111654641;