Genetic Variant ALG9:c.*2479delA (chr11-111783917-GT-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_024740.2(ALG9):c.*2479delA 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

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -1.70

Publications

0 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, G2P
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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024740.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ALG9	NM_024740.2	MANE Select	c.*2479delA	3_prime_UTR	Exon 15 of 15	NP_079016.2	Q9H6U8-3
ALG9	NM_001441203.1		c.*2139delA	3_prime_UTR	Exon 16 of 16	NP_001428132.1
ALG9	NM_001352417.1		c.*2139delA	3_prime_UTR	Exon 16 of 16	NP_001339346.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG9	ENST00000616540.5	TSL:1 MANE Select	c.*2479delA		3_prime_UTR	Exon 15 of 15	ENSP00000482437.1	Q9H6U8-3
	ALG9	ENST00000532425.6	TSL:3	c.*2139delA		3_prime_UTR	Exon 6 of 6	ENSP00000432442.2	H0YCW6

Frequencies

GnomAD3 genomes

AF:

0.0272

AC:

3161

AN:

116140

Hom.:

113

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.0273

AC:

3171

AN:

116202

Hom.:

113

Cov.:

AF XY:

0.0289

AC XY:

1603

AN XY:

55528

show subpopulations

African (AFR)

AF:

0.0831

AC:

2639

AN:

31762

American (AMR)

AF:

0.0120

AC:

126

AN:

10502

Ashkenazi Jewish (ASJ)

AF:

0.000744

AC:

AN:

2688

East Asian (EAS)

AF:

0.00786

AC:

AN:

4198

South Asian (SAS)

AF:

0.0607

AC:

223

AN:

3674

European-Finnish (FIN)

AF:

0.000936

AC:

AN:

6412

Middle Eastern (MID)

AF:

0.0231

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.00184

AC:

100

AN:

54400

Other (OTH)

AF:

0.0240

AC:

AN:

1544

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

138

276

415

553

691

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.000127

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Congenital disorder of glycosylation (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.7

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

11-111783917-GTTT-GTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over