Genetic Variant ALG9:c.1602+10449A>G (chr11-111825716-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_024740.2(ALG9):c.1602+10449A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 152,006 control chromosomes in the GnomAD database, including 31,024 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.64 ( 31024 hom., cov: 31)

Consequence

ALG9
NM_024740.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.765

Publications

1 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 links:

ENSG00000258529 (HGNC:):

ENSG00000258529 links:

ALG9-IT1 (HGNC:41409): (ALG9 intronic transcript 1)

ALG9-IT1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 11-111825716-T-C is Benign according to our data. Variant chr11-111825716-T-C is described in ClinVar as Benign. ClinVar VariationId is 1166805.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.746 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.1602+10449A>G	intron	N/A	NP_079016.2	Q9H6U8-3
ALG9	NM_001441203.1		c.1602+10449A>G	intron	N/A	NP_001428132.1
ALG9	NM_001352417.1		c.1581+10449A>G	intron	N/A	NP_001339346.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ALG9	ENST00000616540.5	TSL:1 MANE Select	c.1602+10449A>G	intron	N/A	ENSP00000482437.1	Q9H6U8-3
ENSG00000258529	ENST00000622211.4	TSL:2	c.2280+10449A>G	intron	N/A	ENSP00000482396.1	A0A087WZ62
ALG9	ENST00000614444.4	TSL:1	c.1581+10449A>G	intron	N/A	ENSP00000484200.1	Q9H6U8-1

Frequencies

GnomAD3 genomes

AF:

0.638

AC:

96951

AN:

151888

Hom.:

31015

Cov.:

show subpopulations

Gnomad AFR

AF:

0.626

Gnomad AMI

AF:

0.722

Gnomad AMR

AF:

0.687

Gnomad ASJ

AF:

0.622

Gnomad EAS

AF:

0.766

Gnomad SAS

AF:

0.640

Gnomad FIN

AF:

0.632

Gnomad MID

AF:

0.693

Gnomad NFE

AF:

0.625

Gnomad OTH

AF:

0.642

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

GnomAD4 genome

AF:

0.638

AC:

97005

AN:

152006

Hom.:

31024

Cov.:

AF XY:

0.643

AC XY:

47781

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.626

AC:

25946

AN:

41434

American (AMR)

AF:

0.687

AC:

10492

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.622

AC:

2158

AN:

3468

East Asian (EAS)

AF:

0.766

AC:

3968

AN:

5178

South Asian (SAS)

AF:

0.640

AC:

3087

AN:

4826

European-Finnish (FIN)

AF:

0.632

AC:

6657

AN:

10528

Middle Eastern (MID)

AF:

0.687

AC:

202

AN:

294

European-Non Finnish (NFE)

AF:

0.625

AC:

42488

AN:

67984

Other (OTH)

AF:

0.640

AC:

1351

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1823

3647

5470

7294

9117

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

796

1592

2388

3184

3980

<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:

0.625

Hom.:

3684

Bravo

AF:

0.642

Asia WGS

AF:

0.668

AC:

2325

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

ALG9 congenital disorder of glycosylation (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.59

(source)

DANN

Benign

0.34

PhyloP100

-0.77

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over