rs9616204

Variant names:

• chr22-49909882-T-C
• rs9616204
• NM_024105.4:c.664+12A>G

Your query was ambiguous. Multiple possible variants found:

• chr22-49909882-T-C
• chr22-49909882-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.67
• Publications: 14 publications found

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)

ACMG classification

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 ClinVar as Benign. ClinVar VariationId 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.

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+12A>G		intron	N/A	NP_077010.1	Q9BV10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG12	ENST00000330817.11	TSL:1 MANE Select	c.664+12A>G		intron	N/A	ENSP00000333813.5	Q9BV10
	ALG12	ENST00000905517.1		c.664+12A>G		intron	N/A	ENSP00000575576.1
	ALG12	ENST00000905518.1		c.664+12A>G		intron	N/A	ENSP00000575577.1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36527 AN: 152076 Hom.: 4851 Cov.: 34

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

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.: 35 AF XY: 0.216 AC XY: 156686 AN XY: 726774

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

GnomAD4 genome AF: 0.240 AC: 36574 AN: 152192 Hom.: 4864 Cov.: 34 AF XY: 0.238 AC XY: 17737 AN XY: 74434

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: 68 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13501 AN: 67982

Other (OTH) AF: 0.218 AC: 461 AN: 2110

Alfa AF: 0.232 Hom.: 1026

Bravo AF: 0.239

Asia WGS AF: 0.277 AC: 964 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	ALG12-congenital disorder of glycosylation (2)
-	-	2	not specified (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.50
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)

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

Other links and lift over

dbSNP: rs9616204; hg19: chr22-50303530;