Variant 22-49913536-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_024105.4(ALG12):c.163-19C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,613,914 control chromosomes in the GnomAD database, including 8,711 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.081 ( 598 hom., cov: 34)

Exomes 𝑓: 0.10 ( 8113 hom. )

Consequence

ALG12
NM_024105.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.302

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 22-49913536-G-T is Benign according to our data. Variant chr22-49913536-G-T is described in ClinVar as [Benign]. Clinvar id is 96096.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
ALG12	NM_024105.4 linkuse as main transcript	c.163-19C>A	intron_variant	ENST00000330817.11	NP_077010.1	Q9BV10A0A024R4V6
ALG12	XM_017028936.2 linkuse as main transcript	c.163-19C>A	intron_variant		XP_016884425.1
ALG12	XM_017028937.2 linkuse as main transcript	c.163-19C>A	intron_variant		XP_016884426.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALG12	ENST00000330817.11 linkuse as main transcript	c.163-19C>A		intron_variant		1	NM_024105.4	ENSP00000333813.5		Q9BV10

Frequencies

GnomAD3 genomes

AF:

0.0814

AC:

12391

AN:

152228

Hom.:

596

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0280

Gnomad AMI

AF:

0.174

Gnomad AMR

AF:

0.0808

Gnomad ASJ

AF:

0.0914

Gnomad EAS

AF:

0.0419

Gnomad SAS

AF:

0.121

Gnomad FIN

AF:

0.113

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.0694

GnomAD3 exomes

AF:

0.0932

AC:

23402

AN:

251224

Hom.:

1196

AF XY:

0.0975

AC XY:

13245

AN XY:

135850

show subpopulations

Gnomad AFR exome

AF:

0.0257

Gnomad AMR exome

AF:

0.0652

Gnomad ASJ exome

AF:

0.101

Gnomad EAS exome

AF:

0.0332

Gnomad SAS exome

AF:

0.130

Gnomad FIN exome

AF:

0.111

Gnomad NFE exome

AF:

0.107

Gnomad OTH exome

AF:

0.0961

GnomAD4 exome

AF:

0.103

AC:

150799

AN:

1461568

Hom.:

8113

Cov.:

AF XY:

0.104

AC XY:

75927

AN XY:

727086

show subpopulations

Gnomad4 AFR exome

AF:

0.0250

Gnomad4 AMR exome

AF:

0.0677

Gnomad4 ASJ exome

AF:

0.0969

Gnomad4 EAS exome

AF:

0.0475

Gnomad4 SAS exome

AF:

0.132

Gnomad4 FIN exome

AF:

0.114

Gnomad4 NFE exome

AF:

0.107

Gnomad4 OTH exome

AF:

0.0973

GnomAD4 genome

AF:

0.0814

AC:

12402

AN:

152346

Hom.:

598

Cov.:

AF XY:

0.0811

AC XY:

6045

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.0279

Gnomad4 AMR

AF:

0.0809

Gnomad4 ASJ

AF:

0.0914

Gnomad4 EAS

AF:

0.0416

Gnomad4 SAS

AF:

0.121

Gnomad4 FIN

AF:

0.113

Gnomad4 NFE

AF:

0.108

Gnomad4 OTH

AF:

0.0729

Alfa

AF:

0.0989

Hom.:

156

Bravo

AF:

0.0737

Asia WGS

AF:

0.0980

AC:

343

AN:

3478

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)	Oct 16, 2012	- -

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:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

8.4

DANN

Benign

0.87

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