11-111849349-C-A

Position:

• chr11-111849349-C-A

Variant summary

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

The NM_024740.2(ALG9):​c.895+4031G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 152,058 control chromosomes in the GnomAD database, including 10,898 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 0.37 (10895 hom., cov: 32)
  • Exomes 𝑓: 0.44 (3 hom.)
• Consequence: ALG9 NM_024740.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.494

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=-0.91).
• 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	Protein	UniProt
ALG9	NM_024740.2	c.895+4031G>T		intron_variant		ENST00000616540.5	NP_079016.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALG9	ENST00000616540.5	c.895+4031G>T		intron_variant		1	NM_024740.2	ENSP00000482437

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56761 AN: 151908 Hom.: 10879 Cov.: 32

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.340

GnomAD4 exome AF: 0.438 AC: 14 AN: 32 Hom.: 3 AF XY: 0.500 AC XY: 13 AN XY: 26

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.374 AC: 56810 AN: 152026 Hom.: 10895 Cov.: 32 AF XY: 0.379 AC XY: 28152 AN XY: 74306

Gnomad4 AFR AF: 0.416

Gnomad4 AMR AF: 0.345

Gnomad4 ASJ AF: 0.257

Gnomad4 EAS AF: 0.586

Gnomad4 SAS AF: 0.391

Gnomad4 FIN AF: 0.380

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.342

Alfa AF: 0.338 Hom.: 8656

Bravo AF: 0.375

Asia WGS AF: 0.438 AC: 1525 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
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: rs1648390; hg19: chr11-111720072;