rs62233155

Positions:

chr22-49904470-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_024105.4(ALG12):c.1029G>A(p.Ala343=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0338 in 1,614,076 control chromosomes in the GnomAD database, including 1,186 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 93 hom., cov: 32)

Exomes 𝑓: 0.035 ( 1093 hom. )

Consequence

ALG12
NM_024105.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.307

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 22-49904470-C-T is Benign according to our data. Variant chr22-49904470-C-T is described in ClinVar as [Benign]. Clinvar id is 342045.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-49904470-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.307 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0269 (4087/152212) while in subpopulation NFE AF= 0.0383 (2604/67998). AF 95% confidence interval is 0.0371. There are 93 homozygotes in gnomad4. There are 2024 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 93 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ALG12	NM_024105.4 linkuse as main transcript	c.1029G>A	p.Ala343=	synonymous_variant	8/10	ENST00000330817.11
ALG12	XM_017028936.2 linkuse as main transcript	c.1029G>A	p.Ala343=	synonymous_variant	8/10
ALG12	XM_017028937.2 linkuse as main transcript	c.1029G>A	p.Ala343=	synonymous_variant	8/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ALG12	ENST00000330817.11 linkuse as main transcript	c.1029G>A	p.Ala343=	synonymous_variant	8/10	1	NM_024105.4	P1
	ENST00000610245.1 linkuse as main transcript	n.2243C>T		non_coding_transcript_exon_variant	1/1
ALG12	ENST00000486602.1 linkuse as main transcript	c.237G>A	p.Ala79=	synonymous_variant	2/4	3
ALG12	ENST00000492791.1 linkuse as main transcript	c.524-86G>A		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0269

AC:

4088

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00630

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0181

Gnomad ASJ

AF:

0.0193

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00415

Gnomad FIN

AF:

0.0764

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0383

Gnomad OTH

AF:

0.0206

GnomAD3 exomes

AF:

0.0301

AC:

7564

AN:

251330

Hom.:

197

AF XY:

0.0300

AC XY:

4076

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.00548

Gnomad AMR exome

AF:

0.00983

Gnomad ASJ exome

AF:

0.0237

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00483

Gnomad FIN exome

AF:

0.0782

Gnomad NFE exome

AF:

0.0428

Gnomad OTH exome

AF:

0.0300

GnomAD4 exome

AF:

0.0345

AC:

50490

AN:

1461864

Hom.:

1093

Cov.:

AF XY:

0.0338

AC XY:

24574

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.00472

Gnomad4 AMR exome

AF:

0.0101

Gnomad4 ASJ exome

AF:

0.0231

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00561

Gnomad4 FIN exome

AF:

0.0791

Gnomad4 NFE exome

AF:

0.0385

Gnomad4 OTH exome

AF:

0.0289

GnomAD4 genome

AF:

0.0269

AC:

4087

AN:

152212

Hom.:

Cov.:

AF XY:

0.0272

AC XY:

2024

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.00628

Gnomad4 AMR

AF:

0.0180

Gnomad4 ASJ

AF:

0.0193

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00415

Gnomad4 FIN

AF:

0.0764

Gnomad4 NFE

AF:

0.0383

Gnomad4 OTH

AF:

0.0203

Alfa

AF:

0.0331

Hom.:

Bravo

AF:

0.0214

Asia WGS

AF:

0.00491

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

ALG12-congenital disorder of glycosylation

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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. -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

- -

ALG12-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 24, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

7.0

DANN

Benign

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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