22-49903598-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.304

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 22-49903598-C-T is Benign according to our data. Variant chr22-49903598-C-T is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
ALG12	NM_024105.4 linkuse as main transcript	c.*240G>A	3_prime_UTR_variant	10/10	ENST00000330817.11
ALG12	XM_017028936.2 linkuse as main transcript	c.1238+581G>A	intron_variant
ALG12	XM_017028937.2 linkuse as main transcript	c.1238+581G>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALG12	ENST00000330817.11 linkuse as main transcript	c.*240G>A		3_prime_UTR_variant	10/10	1	NM_024105.4	P1
	ENST00000610245.1 linkuse as main transcript	n.1371C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.0304

AC:

4626

AN:

152212

Hom.:

211

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.00902

AC:

1247

AN:

138216

Hom.:

AF XY:

0.00785

AC XY:

588

AN XY:

74930

show subpopulations

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 SAS exome

AF:

0.00614

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.:

Cov.:

AF XY:

0.00586

AC XY:

1675

AN XY:

286074

show subpopulations

Gnomad4 AFR exome

AF:

0.101

Gnomad4 AMR exome

AF:

0.00510

Gnomad4 ASJ exome

AF:

0.00259

Gnomad4 EAS exome

AF:

0.0302

Gnomad4 SAS exome

AF:

0.00557

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000277

Gnomad4 OTH exome

AF:

0.00839

GnomAD4 genome

AF:

0.0304

AC:

4634

AN:

152330

Hom.:

212

Cov.:

AF XY:

0.0293

AC XY:

2179

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.102

Gnomad4 AMR

AF:

0.00921

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.0312

Gnomad4 SAS

AF:

0.00663

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.0199

Alfa

AF:

0.0140

Hom.:

Bravo

AF:

0.0335

Asia WGS

AF:

0.0240

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 25, 2021

- -

ALG12-congenital disorder of glycosylation

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

Cadd

Benign

3.8

Dann

Benign

0.69

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

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