rs10502149

Variant names:

• chr11-111836663-T-C
• rs10502149
• NM_024740.2:c.1473-369A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

ALG9 Gene-Disease associations (from GenCC):

• ALG9-associated autosomal dominant polycystic kidney disease

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• ALG9-congenital disorder of glycosylation

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Orphanet
• autosomal dominant polycystic kidney disease

  Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet
• Gillessen-Kaesbach-Nishimura syndrome

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ENSG00000258529 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ALG9	NM_024740.2	c.1473-369A>G		intron_variant	Intron 12 of 14	ENST00000616540.5	NP_079016.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALG9	ENST00000616540.5	c.1473-369A>G		intron_variant	Intron 12 of 14	1	NM_024740.2	ENSP00000482437.1
ENSG00000258529	ENST00000622211.4	c.2151-369A>G		intron_variant	Intron 16 of 18	2		ENSP00000482396.1

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

African (AFR) AF: 0.142 AC: 657 AN: 4624

American (AMR) AF: 0.369 AC: 2390 AN: 6482

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 1088 AN: 4056

East Asian (EAS) AF: 0.593 AC: 4278 AN: 7210

South Asian (SAS) AF: 0.397 AC: 12609 AN: 31726

European-Finnish (FIN) AF: 0.377 AC: 2929 AN: 7764

Middle Eastern (MID) AF: 0.327 AC: 197 AN: 602

European-Non Finnish (NFE) AF: 0.341 AC: 33355 AN: 97676

Other (OTH) AF: 0.350 AC: 2903 AN: 8302

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

African (AFR) AF: 0.142 AC: 5917 AN: 41526

American (AMR) AF: 0.313 AC: 4780 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 897 AN: 3466

East Asian (EAS) AF: 0.586 AC: 3039 AN: 5182

South Asian (SAS) AF: 0.393 AC: 1899 AN: 4828

European-Finnish (FIN) AF: 0.379 AC: 4010 AN: 10574

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.339 AC: 23046 AN: 67984

Other (OTH) AF: 0.282 AC: 596 AN: 2112

Alfa AF: 0.321 Hom.: 7521

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
PhyloP100		-1.4
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: rs10502149; hg19: chr11-111707386;