rs9616204

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024105.4(ALG12):c.664+12A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 1,613,118 control chromosomes in the GnomAD database, including 39,987 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4864 hom., cov: 34)

Exomes 𝑓: 0.21 ( 35123 hom. )

Consequence

ALG12
NM_024105.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.67

Publications

14 publications found

Variant links:

Genes affected

ALG12 (HGNC:19358): (ALG12 alpha-1,6-mannosyltransferase) This gene encodes a member of the glycosyltransferase 22 family. The encoded protein catalyzes the addition of the eighth mannose residue in an alpha-1,6 linkage onto the dolichol-PP-oligosaccharide precursor (dolichol-PP-Man(7)GlcNAc(2)) required for protein glycosylation. Mutations in this gene have been associated with congenital disorder of glycosylation type Ig (CDG-Ig)characterized by abnormal N-glycosylation. [provided by RefSeq, Jul 2008]

ALG12 Gene-Disease associations (from GenCC):

ALG12-congenital disorder of glycosylation
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, G2P, ClinGen, Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet

ALG12 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.03).

BP6

Variant 22-49909882-T-C is Benign according to our data. Variant chr22-49909882-T-C is described in CliVar as Benign. Clinvar id is 96098.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-49909882-T-C is described in CliVar as Benign. Clinvar id is 96098.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-49909882-T-C is described in CliVar as Benign. Clinvar id is 96098.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-49909882-T-C is described in CliVar as Benign. Clinvar id is 96098.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-49909882-T-C is described in CliVar as Benign. Clinvar id is 96098.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-49909882-T-C is described in CliVar as Benign. Clinvar id is 96098.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-49909882-T-C is described in CliVar as Benign. Clinvar id is 96098.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-49909882-T-C is described in CliVar as Benign. Clinvar id is 96098.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-49909882-T-C is described in CliVar as Benign. Clinvar id is 96098.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ALG12	NM_024105.4 link	c.664+12A>G	intron_variant	Intron 5 of 9	ENST00000330817.11	NP_077010.1	Q9BV10A0A024R4V6
ALG12	XM_017028936.2 link	c.664+12A>G	intron_variant	Intron 5 of 9		XP_016884425.1
ALG12	XM_017028937.2 link	c.664+12A>G	intron_variant	Intron 5 of 10		XP_016884426.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALG12	ENST00000330817.11 link	c.664+12A>G		intron_variant	Intron 5 of 9	1	NM_024105.4	ENSP00000333813.5		Q9BV10
ALG12	ENST00000492791.1 link	n.193+12A>G		intron_variant	Intron 1 of 5	3		ENSP00000417387.1		H7C4I6

Frequencies

GnomAD3 genomes

AF:

0.240

AC:

36527

AN:

152076

Hom.:

4851

Cov.:

show subpopulations

Gnomad AFR

AF:

0.351

Gnomad AMI

AF:

0.390

Gnomad AMR

AF:

0.169

Gnomad ASJ

AF:

0.287

Gnomad EAS

AF:

0.0912

Gnomad SAS

AF:

0.394

Gnomad FIN

AF:

0.158

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.199

Gnomad OTH

AF:

0.214

GnomAD2 exomes

AF:

0.215

AC:

53814

AN:

250762

AF XY:

0.225

show subpopulations

Gnomad AFR exome

AF:

0.358

Gnomad AMR exome

AF:

0.122

Gnomad ASJ exome

AF:

0.289

Gnomad EAS exome

AF:

0.0825

Gnomad FIN exome

AF:

0.156

Gnomad NFE exome

AF:

0.196

Gnomad OTH exome

AF:

0.205

GnomAD4 exome

AF:

0.209

AC:

305606

AN:

1460926

Hom.:

35123

Cov.:

AF XY:

0.216

AC XY:

156686

AN XY:

726774

show subpopulations

African (AFR)

AF:

0.366

AC:

12244

AN:

33466

American (AMR)

AF:

0.128

AC:

5719

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.282

AC:

7370

AN:

26124

East Asian (EAS)

AF:

0.0919

AC:

3648

AN:

39676

South Asian (SAS)

AF:

0.410

AC:

35326

AN:

86220

European-Finnish (FIN)

AF:

0.161

AC:

8587

AN:

53282

Middle Eastern (MID)

AF:

0.274

AC:

1580

AN:

5766

European-Non Finnish (NFE)

AF:

0.196

AC:

217920

AN:

1111332

Other (OTH)

AF:

0.219

AC:

13212

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.439

Heterozygous variant carriers

13768

27536

41305

55073

68841

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7726

15452

23178

30904

38630

<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:

0.240

AC:

36574

AN:

152192

Hom.:

4864

Cov.:

AF XY:

0.238

AC XY:

17737

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.351

AC:

14560

AN:

41500

American (AMR)

AF:

0.169

AC:

2588

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.287

AC:

996

AN:

3466

East Asian (EAS)

AF:

0.0908

AC:

471

AN:

5188

South Asian (SAS)

AF:

0.393

AC:

1898

AN:

4828

European-Finnish (FIN)

AF:

0.158

AC:

1677

AN:

10610

Middle Eastern (MID)

AF:

0.231

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.199

AC:

13501

AN:

67982

Other (OTH)

AF:

0.218

AC:

461

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1456

2912

4369

5825

7281

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

374

748

1122

1496

1870

<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:

0.232

Hom.:

1026

Bravo

AF:

0.239

Asia WGS

AF:

0.277

AC:

964

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Jul 10, 2012

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

ALG12-congenital disorder of glycosylation

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.50

(source)

DANN

Benign

0.22

PhyloP100

-1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over