rs8135963

Positions:

chr22-49907828-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_024105.4(ALG12):c.885A>G(p.Ala295=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 1,613,820 control chromosomes in the GnomAD database, including 59,745 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 13919 hom., cov: 32)

Exomes 𝑓: 0.23 ( 45826 hom. )

Consequence

ALG12
NM_024105.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -5.39

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 22-49907828-T-C is Benign according to our data. Variant chr22-49907828-T-C is described in ClinVar as [Benign]. Clinvar id is 96102.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-49907828-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-5.39 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ALG12	NM_024105.4 linkuse as main transcript	c.885A>G	p.Ala295=	synonymous_variant	7/10	ENST00000330817.11
ALG12	XM_017028936.2 linkuse as main transcript	c.885A>G	p.Ala295=	synonymous_variant	7/10
ALG12	XM_017028937.2 linkuse as main transcript	c.885A>G	p.Ala295=	synonymous_variant	7/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ALG12	ENST00000330817.11 linkuse as main transcript	c.885A>G	p.Ala295=	synonymous_variant	7/10	1	NM_024105.4	P1
ALG12	ENST00000486602.1 linkuse as main transcript	c.93A>G	p.Ala31=	synonymous_variant	1/4	3
ALG12	ENST00000492791.1 linkuse as main transcript	c.417A>G	p.Ala139=	synonymous_variant, NMD_transcript_variant	3/6	3

Frequencies

GnomAD3 genomes

AF:

0.358

AC:

54348

AN:

151950

Hom.:

13859

Cov.:

show subpopulations

Gnomad AFR

AF:

0.729

Gnomad AMI

AF:

0.468

Gnomad AMR

AF:

0.223

Gnomad ASJ

AF:

0.303

Gnomad EAS

AF:

0.146

Gnomad SAS

AF:

0.411

Gnomad FIN

AF:

0.167

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.207

Gnomad OTH

AF:

0.306

GnomAD3 exomes

AF:

0.256

AC:

64213

AN:

251256

Hom.:

11252

AF XY:

0.258

AC XY:

35082

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.742

Gnomad AMR exome

AF:

0.152

Gnomad ASJ exome

AF:

0.305

Gnomad EAS exome

AF:

0.134

Gnomad SAS exome

AF:

0.426

Gnomad FIN exome

AF:

0.165

Gnomad NFE exome

AF:

0.205

Gnomad OTH exome

AF:

0.233

GnomAD4 exome

AF:

0.229

AC:

334278

AN:

1461752

Hom.:

45826

Cov.:

AF XY:

0.234

AC XY:

170123

AN XY:

727166

show subpopulations

Gnomad4 AFR exome

AF:

0.753

Gnomad4 AMR exome

AF:

0.160

Gnomad4 ASJ exome

AF:

0.297

Gnomad4 EAS exome

AF:

0.138

Gnomad4 SAS exome

AF:

0.425

Gnomad4 FIN exome

AF:

0.169

Gnomad4 NFE exome

AF:

0.203

Gnomad4 OTH exome

AF:

0.256

GnomAD4 genome

AF:

0.358

AC:

54463

AN:

152068

Hom.:

13919

Cov.:

AF XY:

0.354

AC XY:

26284

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.729

Gnomad4 AMR

AF:

0.223

Gnomad4 ASJ

AF:

0.303

Gnomad4 EAS

AF:

0.146

Gnomad4 SAS

AF:

0.410

Gnomad4 FIN

AF:

0.167

Gnomad4 NFE

AF:

0.207

Gnomad4 OTH

AF:

0.310

Alfa

AF:

0.243

Hom.:

7458

Bravo

AF:

0.370

Asia WGS

AF:

0.331

AC:

1152

AN:

3476

EpiCase

AF:

0.204

EpiControl

AF:

0.211

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 25, 2012	- -

ALG12-congenital disorder of glycosylation

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
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. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.16

DANN

Benign

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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