rs76848348

Variant names:

• chr22-49903598-C-T
• rs76848348
• NM_024105.4:c.*240G>A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_024105.4(ALG12):​c.*240G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 680,138 control chromosomes in the GnomAD database, including 308 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (212 hom., cov: 33)
  • Exomes 𝑓: 0.0064 (96 hom.)
• Consequence: ALG12 NM_024105.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.304
• Publications: 3 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: PanelApp Australia, Orphanet, Ambry Genetics, G2P, ClinGen, Labcorp Genetics (formerly Invitae)

ENSG00000273192 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.041).
• BP6: Variant 22-49903598-C-T is Benign according to our data. Variant chr22-49903598-C-T is described in ClinVar as Benign. ClinVar VariationId is 342036.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0991 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.*240G>A		3_prime_UTR	Exon 10 of 10	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.*240G>A		3_prime_UTR	Exon 10 of 10	ENSP00000333813.5	Q9BV10
	ALG12	ENST00000905517.1		c.*240G>A		3_prime_UTR	Exon 10 of 10	ENSP00000575576.1
	ALG12	ENST00000905518.1		c.*240G>A		3_prime_UTR	Exon 10 of 10	ENSP00000575577.1

Frequencies

GnomAD3 genomes AF: 0.0304 AC: 4626 AN: 152212 Hom.: 211 Cov.: 33

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00922

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.0312

Gnomad SAS AF: 0.00662

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.0201

GnomAD2 exomes AF: 0.00902 AC: 1247 AN: 138216 AF XY: 0.00785

Gnomad AFR exome AF: 0.103

Gnomad AMR exome AF: 0.00462

Gnomad ASJ exome AF: 0.00315

Gnomad EAS exome AF: 0.0248

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000342

Gnomad OTH exome AF: 0.00550

GnomAD4 exome AF: 0.00639 AC: 3371 AN: 527808 Hom.: 96 Cov.: 4 AF XY: 0.00586 AC XY: 1675 AN XY: 286074

African (AFR) AF: 0.101 AC: 1541 AN: 15310

American (AMR) AF: 0.00510 AC: 172 AN: 33742

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 50 AN: 19330

East Asian (EAS) AF: 0.0302 AC: 912 AN: 30150

South Asian (SAS) AF: 0.00557 AC: 344 AN: 61732

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31138

Middle Eastern (MID) AF: 0.00606 AC: 24 AN: 3958

European-Non Finnish (NFE) AF: 0.000277 AC: 84 AN: 303368

Other (OTH) AF: 0.00839 AC: 244 AN: 29080

GnomAD4 genome AF: 0.0304 AC: 4634 AN: 152330 Hom.: 212 Cov.: 33 AF XY: 0.0293 AC XY: 2179 AN XY: 74488

African (AFR) AF: 0.102 AC: 4226 AN: 41556

American (AMR) AF: 0.00921 AC: 141 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3470

East Asian (EAS) AF: 0.0312 AC: 162 AN: 5188

South Asian (SAS) AF: 0.00663 AC: 32 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000323 AC: 22 AN: 68032

Other (OTH) AF: 0.0199 AC: 42 AN: 2114

Alfa AF: 0.0203 Hom.: 36

Bravo AF: 0.0335

Asia WGS AF: 0.0240 AC: 82 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.8
DANN	Benign	0.69
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: rs76848348; hg19: chr22-50297246;