Genetic Variant ALG9:n.4035C>G (chr11-111769896-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The XR_001747967.3(ALG9):n.4035C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0871 in 152,050 control chromosomes in the GnomAD database, including 1,893 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 0.087 ( 1893 hom., cov: 32)

Consequence

ALG9
XR_001747967.3 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.165

Publications

2 publications found

Variant links:

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

ALG9 links:

ENSG00000254990 (HGNC:):

ENSG00000254990 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALG9	XR_001747967.3 link	n.4035C>G		non_coding_transcript_exon_variant	Exon 19 of 19
ALG9	XR_001747968.3 link	n.2710-757C>G		intron_variant	Intron 20 of 20

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
ENSG00000254990	ENST00000529841.6 link	n.298-444C>G	intron_variant	Intron 2 of 3	3
ENSG00000254990	ENST00000534218.2 link	n.330-757C>G	intron_variant	Intron 3 of 3	2
ENSG00000254990	ENST00000822974.1 link	n.191-757C>G	intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.0870

AC:

13219

AN:

151932

Hom.:

1887

Cov.:

show subpopulations

Gnomad AFR

AF:

0.301

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0354

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00162

Gnomad OTH

AF:

0.0656

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0871

AC:

13250

AN:

152050

Hom.:

1893

Cov.:

AF XY:

0.0847

AC XY:

6297

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.301

AC:

12437

AN:

41372

American (AMR)

AF:

0.0354

AC:

540

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00548

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000622

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0000944

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00162

AC:

110

AN:

68020

Other (OTH)

AF:

0.0649

AC:

137

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

465

930

1395

1860

2325

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

228

342

456

570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0129

Hom.:

Bravo

AF:

0.100

Asia WGS

AF:

0.0180

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

3.3

(source)

DANN

Benign

0.51

PhyloP100

0.17

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over