chr22-49904240-T-C

Position:

chr22-49904240-T-C

Variant summary

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

The NM_024105.4(ALG12):c.1177A>G(p.Ile393Val) variant causes a missense change. The variant allele was found at a frequency of 0.114 in 1,614,008 control chromosomes in the GnomAD database, including 11,273 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.094 ( 772 hom., cov: 32)

Exomes 𝑓: 0.12 ( 10501 hom. )

Consequence

ALG12
NM_024105.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 5.02

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 (MetaRNN=0.0070717633).

BP6

Variant 22-49904240-T-C is Benign according to our data. Variant chr22-49904240-T-C is described in ClinVar as [Benign]. Clinvar id is 96095.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ALG12	NM_024105.4 linkuse as main transcript	c.1177A>G	p.Ile393Val	missense_variant	9/10	ENST00000330817.11	NP_077010.1
ALG12	XM_017028936.2 linkuse as main transcript	c.1177A>G	p.Ile393Val	missense_variant	9/10		XP_016884425.1
ALG12	XM_017028937.2 linkuse as main transcript	c.1177A>G	p.Ile393Val	missense_variant	9/11		XP_016884426.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ALG12	ENST00000330817.11 linkuse as main transcript	c.1177A>G	p.Ile393Val	missense_variant	9/10	1	NM_024105.4	ENSP00000333813	P1
	ENST00000610245.1 linkuse as main transcript	n.2013T>C		non_coding_transcript_exon_variant	1/1
ALG12	ENST00000486602.1 linkuse as main transcript	c.385A>G	p.Ile129Val	missense_variant	3/4	3		ENSP00000420630
ALG12	ENST00000492791.1 linkuse as main transcript	c.587A>G	p.His196Arg	missense_variant, NMD_transcript_variant	5/6	3		ENSP00000417387

Frequencies

GnomAD3 genomes

AF:

0.0943

AC:

14336

AN:

152042

Hom.:

763

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0451

Gnomad AMI

AF:

0.174

Gnomad AMR

AF:

0.0851

Gnomad ASJ

AF:

0.146

Gnomad EAS

AF:

0.0428

Gnomad SAS

AF:

0.189

Gnomad FIN

AF:

0.122

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.116

Gnomad OTH

AF:

0.0790

GnomAD3 exomes

AF:

0.110

AC:

27722

AN:

251308

Hom.:

1786

AF XY:

0.117

AC XY:

15903

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.0413

Gnomad AMR exome

AF:

0.0694

Gnomad ASJ exome

AF:

0.151

Gnomad EAS exome

AF:

0.0341

Gnomad SAS exome

AF:

0.198

Gnomad FIN exome

AF:

0.123

Gnomad NFE exome

AF:

0.115

Gnomad OTH exome

AF:

0.109

GnomAD4 exome

AF:

0.116

AC:

169387

AN:

1461848

Hom.:

10501

Cov.:

AF XY:

0.119

AC XY:

86392

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.0420

Gnomad4 AMR exome

AF:

0.0720

Gnomad4 ASJ exome

AF:

0.147

Gnomad4 EAS exome

AF:

0.0482

Gnomad4 SAS exome

AF:

0.199

Gnomad4 FIN exome

AF:

0.125

Gnomad4 NFE exome

AF:

0.115

Gnomad4 OTH exome

AF:

0.113

GnomAD4 genome

AF:

0.0944

AC:

14362

AN:

152160

Hom.:

772

Cov.:

AF XY:

0.0949

AC XY:

7060

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0455

Gnomad4 AMR

AF:

0.0852

Gnomad4 ASJ

AF:

0.146

Gnomad4 EAS

AF:

0.0425

Gnomad4 SAS

AF:

0.189

Gnomad4 FIN

AF:

0.122

Gnomad4 NFE

AF:

0.116

Gnomad4 OTH

AF:

0.0825

Alfa

AF:

0.109

Hom.:

1532

Bravo

AF:

0.0850

TwinsUK

AF:

0.115

AC:

428

ALSPAC

AF:

0.111

AC:

428

ESP6500AA

AF:

0.0456

AC:

201

ESP6500EA

AF:

0.115

AC:

987

ExAC

AF:

0.112

AC:

13597

Asia WGS

AF:

0.129

AC:

452

AN:

3478

EpiCase

AF:

0.112

EpiControl

AF:

0.114

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 16, 2012	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 16, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

ALG12-congenital disorder of glycosylation

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.78

MetaRNN

Benign

0.0071

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

5.8e-7

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.93

REVEL

Benign

0.20

Sift

Pathogenic

0.0

Sift4G

Benign

0.12

Polyphen

1.0

Vest4

0.069

MPC

0.51

ClinPred

0.072

GERP RS

4.3

Varity_R

0.30

gMVP

0.66

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