chr22-49903787-T-C

Variant names:

• chr22-49903787-T-C
• rs1321
• NM_024105.4:c.*51A>G

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.*51A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 1,578,790 control chromosomes in the GnomAD database, including 58,813 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (13931 hom., cov: 33)
  • Exomes 𝑓: 0.23 (44882 hom.)
• Consequence: ALG12 NM_024105.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.243
• Publications: 41 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: Ambry Genetics, G2P, ClinGen, Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet

ENSG00000273192 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (REVEL=0.027).
• BP6: Variant 22-49903787-T-C is Benign according to our data. Variant chr22-49903787-T-C is described in ClinVar as Benign. ClinVar VariationId is 342038.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.723 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG12	NM_024105.4	MANE Select	c.*51A>G		3_prime_UTR	Exon 10 of 10	NP_077010.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG12	ENST00000330817.11	TSL:1 MANE Select	c.*51A>G		3_prime_UTR	Exon 10 of 10	ENSP00000333813.5
	ALG12	ENST00000486602.1	TSL:3	c.536A>G	p.His179Arg	missense	Exon 4 of 4	ENSP00000420630.1
	ENSG00000273192	ENST00000610245.1	TSL:6	n.1560T>C		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54366 AN: 152056 Hom.: 13872 Cov.: 33

Gnomad AFR AF: 0.729

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.306

GnomAD2 exomes AF: 0.254 AC: 63079 AN: 248116 AF XY: 0.259

Gnomad AFR exome AF: 0.744

Gnomad AMR exome AF: 0.152

Gnomad ASJ exome AF: 0.305

Gnomad EAS exome AF: 0.133

Gnomad FIN exome AF: 0.165

Gnomad NFE exome AF: 0.205

Gnomad OTH exome AF: 0.232

GnomAD4 exome AF: 0.229 AC: 326462 AN: 1426616 Hom.: 44882 Cov.: 27 AF XY: 0.234 AC XY: 166766 AN XY: 711634

African (AFR) AF: 0.753 AC: 24710 AN: 32824

American (AMR) AF: 0.160 AC: 7149 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 7704 AN: 25914

East Asian (EAS) AF: 0.137 AC: 5425 AN: 39464

South Asian (SAS) AF: 0.426 AC: 36481 AN: 85542

European-Finnish (FIN) AF: 0.169 AC: 8912 AN: 52836

Middle Eastern (MID) AF: 0.327 AC: 1861 AN: 5688

European-Non Finnish (NFE) AF: 0.203 AC: 219059 AN: 1080484

Other (OTH) AF: 0.256 AC: 15161 AN: 59206

GnomAD4 genome AF: 0.358 AC: 54480 AN: 152174 Hom.: 13931 Cov.: 33 AF XY: 0.353 AC XY: 26275 AN XY: 74400

African (AFR) AF: 0.729 AC: 30285 AN: 41518

American (AMR) AF: 0.223 AC: 3408 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1055 AN: 3472

East Asian (EAS) AF: 0.145 AC: 748 AN: 5160

South Asian (SAS) AF: 0.412 AC: 1987 AN: 4826

European-Finnish (FIN) AF: 0.166 AC: 1766 AN: 10612

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14069 AN: 67980

Other (OTH) AF: 0.310 AC: 654 AN: 2110

Alfa AF: 0.266 Hom.: 14228

Bravo AF: 0.370

Asia WGS AF: 0.332 AC: 1157 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	-0.93
CADD	Benign	1.1
DANN	Benign	0.21
PhyloP100		-0.24
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: rs1321; hg19: chr22-50297435; COSMIC: COSV58206677; COSMIC: COSV58206677;