chr11-111871354-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP6_ModerateBP7

The NM_024740.2(ALG9):c.129C>T(p.Thr43Thr) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000984 in 1,524,218 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

ALG9
NM_024740.2 splice_region, synonymous

Scores

Splicing: ADA: 0.0001369

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.935

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: 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:

ENSG00000258529 (HGNC:):

ENSG00000258529 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

BP6

Variant 11-111871354-G-A is Benign according to our data. Variant chr11-111871354-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 538564.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.935 with no splicing effect.

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	HGVSp	Effect	Exon Rank	Protein
ALG9	NM_024740.2	MANE Select	c.129C>T	p.Thr43Thr	splice_region synonymous	Exon 1 of 15	NP_079016.2
ALG9	NM_001352413.1		c.-389C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 15	NP_001339342.1
ALG9	NM_001352409.1		c.-246C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 14	NP_001339338.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ALG9	ENST00000616540.5	TSL:1 MANE Select	c.129C>T	p.Thr43Thr	splice_region synonymous	Exon 1 of 15	ENSP00000482437.1
ENSG00000258529	ENST00000622211.4	TSL:2	c.828C>T	p.Thr276Thr	splice_region synonymous	Exon 5 of 19	ENSP00000482396.1
ALG9	ENST00000614444.4	TSL:1	c.129C>T	p.Thr43Thr	splice_region synonymous	Exon 1 of 15	ENSP00000484200.1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152042

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000791

AC:

AN:

126368

AF XY:

0.0000288

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000427

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000102

AC:

AN:

1372176

Hom.:

Cov.:

AF XY:

0.00000591

AC XY:

AN XY:

676722

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30440

American (AMR)

AF:

0.000343

AC:

AN:

34952

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24788

East Asian (EAS)

AF:

0.00

AC:

AN:

35000

South Asian (SAS)

AF:

0.00

AC:

AN:

78254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33648

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4154

European-Non Finnish (NFE)

AF:

9.31e-7

AC:

AN:

1073740

Other (OTH)

AF:

0.0000175

AC:

AN:

57200

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152042

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41402

American (AMR)

AF:

0.00

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67970

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ALG9 congenital disorder of glycosylation

Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Uncertain

0.040

CADD

Benign

7.4

(source)

DANN

Benign

0.95

PhyloP100

-0.94

PromoterAI

0.018

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00014

dbscSNV1_RF

Benign

0.24

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over