22-49913536-G-T

Variant names:

• chr22-49913536-G-T
• rs11705497
• NM_024105.4:c.163-19C>A

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.163-19C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,613,914 control chromosomes in the GnomAD database, including 8,711 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.081 (598 hom., cov: 34)
  • Exomes 𝑓: 0.10 (8113 hom.)
• Consequence: ALG12 NM_024105.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.302
• Publications: 7 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=-0.79).
• BP6: Variant 22-49913536-G-T is Benign according to our data. Variant chr22-49913536-G-T is described in ClinVar as Benign. ClinVar VariationId is 96096.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.113 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.163-19C>A		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.163-19C>A		intron	N/A	ENSP00000333813.5	Q9BV10
	ALG12	ENST00000905517.1		c.163-19C>A		intron	N/A	ENSP00000575576.1
	ALG12	ENST00000905518.1		c.163-19C>A		intron	N/A	ENSP00000575577.1

Frequencies

GnomAD3 genomes AF: 0.0814 AC: 12391 AN: 152228 Hom.: 596 Cov.: 34

Gnomad AFR AF: 0.0280

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.0808

Gnomad ASJ AF: 0.0914

Gnomad EAS AF: 0.0419

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0694

GnomAD2 exomes AF: 0.0932 AC: 23402 AN: 251224 AF XY: 0.0975

Gnomad AFR exome AF: 0.0257

Gnomad AMR exome AF: 0.0652

Gnomad ASJ exome AF: 0.101

Gnomad EAS exome AF: 0.0332

Gnomad FIN exome AF: 0.111

Gnomad NFE exome AF: 0.107

Gnomad OTH exome AF: 0.0961

GnomAD4 exome AF: 0.103 AC: 150799 AN: 1461568 Hom.: 8113 Cov.: 33 AF XY: 0.104 AC XY: 75927 AN XY: 727086

African (AFR) AF: 0.0250 AC: 837 AN: 33480

American (AMR) AF: 0.0677 AC: 3027 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0969 AC: 2533 AN: 26136

East Asian (EAS) AF: 0.0475 AC: 1885 AN: 39698

South Asian (SAS) AF: 0.132 AC: 11351 AN: 86248

European-Finnish (FIN) AF: 0.114 AC: 6047 AN: 53118

Middle Eastern (MID) AF: 0.0798 AC: 460 AN: 5768

European-Non Finnish (NFE) AF: 0.107 AC: 118785 AN: 1112008

Other (OTH) AF: 0.0973 AC: 5874 AN: 60390

GnomAD4 genome AF: 0.0814 AC: 12402 AN: 152346 Hom.: 598 Cov.: 34 AF XY: 0.0811 AC XY: 6045 AN XY: 74504

African (AFR) AF: 0.0279 AC: 1162 AN: 41588

American (AMR) AF: 0.0809 AC: 1239 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0914 AC: 317 AN: 3470

East Asian (EAS) AF: 0.0416 AC: 216 AN: 5190

South Asian (SAS) AF: 0.121 AC: 587 AN: 4832

European-Finnish (FIN) AF: 0.113 AC: 1200 AN: 10626

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7347 AN: 68014

Other (OTH) AF: 0.0729 AC: 154 AN: 2112

Alfa AF: 0.0971 Hom.: 156

Bravo AF: 0.0737

Asia WGS AF: 0.0980 AC: 343 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.4
DANN	Benign	0.87
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11705497; hg19: chr22-50307184; COSMIC: COSV58208812; COSMIC: COSV58208812;