dbSNP rs9616368: ALG12:c.664+9G>C (chr22-49909885-C-G) – ACMG Classification: Benign (-20 pts)

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+9G>C 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 1,613,232 control chromosomes in the GnomAD database, including 39,979 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 ( 35115 hom. )

Consequence

ALG12
NM_024105.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.205

Publications

17 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: ClinGen, Orphanet, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

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=-0.84).

BP6

Variant 22-49909885-C-G is Benign according to our data. Variant chr22-49909885-C-G is described in ClinVar as Benign. ClinVar VariationId is 96099.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024105.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG12	NM_024105.4	MANE Select	c.664+9G>C		intron	N/A	NP_077010.1	Q9BV10

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ALG12	ENST00000330817.11	TSL:1 MANE Select	c.664+9G>C	intron	N/A	ENSP00000333813.5	Q9BV10
ALG12	ENST00000905517.1		c.664+9G>C	intron	N/A	ENSP00000575576.1
ALG12	ENST00000905518.1		c.664+9G>C	intron	N/A	ENSP00000575577.1

Frequencies

GnomAD3 genomes

AF:

0.240

AC:

36530

AN:

152068

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:

0.0911

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:

53811

AN:

250768

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:

0.0824

Gnomad FIN exome

AF:

0.156

Gnomad NFE exome

AF:

0.196

Gnomad OTH exome

AF:

0.205

GnomAD4 exome

AF:

0.209

AC:

305664

AN:

1461048

Hom.:

35115

Cov.:

AF XY:

0.216

AC XY:

156706

AN XY:

726820

show subpopulations

African (AFR)

AF:

0.366

AC:

12242

AN:

33462

American (AMR)

AF:

0.128

AC:

5720

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.282

AC:

7372

AN:

26126

East Asian (EAS)

AF:

0.0919

AC:

3648

AN:

39678

South Asian (SAS)

AF:

0.410

AC:

35329

AN:

86226

European-Finnish (FIN)

AF:

0.161

AC:

8588

AN:

53280

Middle Eastern (MID)

AF:

0.274

AC:

1582

AN:

5768

European-Non Finnish (NFE)

AF:

0.196

AC:

217966

AN:

1111436

Other (OTH)

AF:

0.219

AC:

13217

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.441

Heterozygous variant carriers

13835

27670

41505

55340

69175

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7728

15456

23184

30912

38640

<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:

36577

AN:

152184

Hom.:

4864

Cov.:

AF XY:

0.238

AC XY:

17739

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.351

AC:

14562

AN:

41486

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:

5190

South Asian (SAS)

AF:

0.393

AC:

1898

AN:

4826

European-Finnish (FIN)

AF:

0.158

AC:

1676

AN:

10606

Middle Eastern (MID)

AF:

0.231

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.199

AC:

13503

AN:

67990

Other (OTH)

AF:

0.218

AC:

461

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1450

2900

4351

5801

7251

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:

0.219

Hom.:

1252

Bravo

AF:

0.239

Asia WGS

AF:

0.277

AC:

964

AN:

3478

EpiCase

AF:

0.194

EpiControl

AF:

0.200

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

ALG12-congenital disorder of glycosylation (2)

not specified (2)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.2

(source)

DANN

Benign

0.33

PhyloP100

-0.20

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=98/2

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over