Genetic Variant ALG12:c.-159_-158delGT (chr22-49918341-AAC-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_024105.4(ALG12):c.-159_-158delGT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 153,378 control chromosomes in the GnomAD database, including 4,597 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.23 ( 4560 hom., cov: 27)

Exomes 𝑓: 0.21 ( 37 hom. )

Consequence

ALG12
NM_024105.4 5_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.71

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 links:

CRELD2 (HGNC:28150): (cysteine rich with EGF like domains 2) Predicted to enable calcium ion binding activity and protein disulfide isomerase activity. Predicted to be located in Golgi apparatus; endoplasmic reticulum; and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

CRELD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 22-49918341-AAC-A is Benign according to our data. Variant chr22-49918341-AAC-A is described in ClinVar as [Likely_benign]. Clinvar id is 342067.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ALG12	NM_024105.4 link	c.-159_-158delGT	5_prime_UTR_variant	Exon 1 of 10	ENST00000330817.11	NP_077010.1	Q9BV10A0A024R4V6
ALG12	XM_017028936.2 link	c.-159_-158delGT	5_prime_UTR_variant	Exon 1 of 10		XP_016884425.1
ALG12	XM_017028937.2 link	c.-159_-158delGT	5_prime_UTR_variant	Exon 1 of 11		XP_016884426.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALG12	ENST00000330817.11 link	c.-159_-158delGT		5_prime_UTR_variant	Exon 1 of 10	1	NM_024105.4	ENSP00000333813.5		Q9BV10
CRELD2	ENST00000450207 link	c.-99_-98delCA		5_prime_UTR_variant	Exon 1 of 7	5		ENSP00000387769.1		A6PWM2

Frequencies

GnomAD3 genomes

AF:

0.232

AC:

35282

AN:

151822

Hom.:

4546

Cov.:

show subpopulations

Gnomad AFR

AF:

0.349

Gnomad AMI

AF:

0.392

Gnomad AMR

AF:

0.164

Gnomad ASJ

AF:

0.236

Gnomad EAS

AF:

0.0897

Gnomad SAS

AF:

0.332

Gnomad FIN

AF:

0.150

Gnomad MID

AF:

0.258

Gnomad NFE

AF:

0.192

Gnomad OTH

AF:

0.209

GnomAD4 exome

AF:

0.215

AC:

311

AN:

1448

Hom.:

AF XY:

0.227

AC XY:

171

AN XY:

752

show subpopulations

Gnomad4 AFR exome

AF:

0.409

Gnomad4 AMR exome

AF:

0.125

Gnomad4 ASJ exome

AF:

0.242

Gnomad4 EAS exome

AF:

0.122

Gnomad4 SAS exome

AF:

0.423

Gnomad4 FIN exome

AF:

0.148

Gnomad4 NFE exome

AF:

0.216

Gnomad4 OTH exome

AF:

0.192

GnomAD4 genome

AF:

0.233

AC:

35329

AN:

151930

Hom.:

4560

Cov.:

AF XY:

0.230

AC XY:

17055

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.349

Gnomad4 AMR

AF:

0.164

Gnomad4 ASJ

AF:

0.236

Gnomad4 EAS

AF:

0.0892

Gnomad4 SAS

AF:

0.332

Gnomad4 FIN

AF:

0.150

Gnomad4 NFE

AF:

0.192

Gnomad4 OTH

AF:

0.214

Alfa

AF:

0.218

Hom.:

473

Bravo

AF:

0.232

Asia WGS

AF:

0.243

AC:

841

AN:

3466

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Congenital disorder of glycosylation

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over