rs78916708

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_024105.4(ALG12):c.469+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0177 in 1,612,618 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 22 hom., cov: 33)

Exomes 𝑓: 0.018 ( 286 hom. )

Consequence

ALG12
NM_024105.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.453

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 22-49910421-G-A is Benign according to our data. Variant chr22-49910421-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 261686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0134 (2047/152358) while in subpopulation EAS AF= 0.0248 (129/5192). AF 95% confidence interval is 0.0214. There are 22 homozygotes in gnomad4. There are 1026 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
ALG12	NM_024105.4 linkuse as main transcript	c.469+13C>T	intron_variant	ENST00000330817.11	NP_077010.1	Q9BV10A0A024R4V6
ALG12	XM_017028936.2 linkuse as main transcript	c.469+13C>T	intron_variant		XP_016884425.1
ALG12	XM_017028937.2 linkuse as main transcript	c.469+13C>T	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.469+13C>T		intron_variant		1	NM_024105.4	ENSP00000333813.5		Q9BV10

Frequencies

GnomAD3 genomes

AF:

0.0135

AC:

2048

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00345

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.0107

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.0248

Gnomad SAS

AF:

0.00497

Gnomad FIN

AF:

0.0323

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0177

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.0160

AC:

3949

AN:

247344

Hom.:

AF XY:

0.0156

AC XY:

2097

AN XY:

134238

show subpopulations

Gnomad AFR exome

AF:

0.00282

Gnomad AMR exome

AF:

0.0130

Gnomad ASJ exome

AF:

0.00181

Gnomad EAS exome

AF:

0.0229

Gnomad SAS exome

AF:

0.00475

Gnomad FIN exome

AF:

0.0303

Gnomad NFE exome

AF:

0.0190

Gnomad OTH exome

AF:

0.0204

GnomAD4 exome

AF:

0.0182

AC:

26523

AN:

1460260

Hom.:

286

Cov.:

AF XY:

0.0177

AC XY:

12854

AN XY:

726388

show subpopulations

Gnomad4 AFR exome

AF:

0.00278

Gnomad4 AMR exome

AF:

0.0127

Gnomad4 ASJ exome

AF:

0.00145

Gnomad4 EAS exome

AF:

0.0405

Gnomad4 SAS exome

AF:

0.00515

Gnomad4 FIN exome

AF:

0.0320

Gnomad4 NFE exome

AF:

0.0190

Gnomad4 OTH exome

AF:

0.0159

GnomAD4 genome

AF:

0.0134

AC:

2047

AN:

152358

Hom.:

Cov.:

AF XY:

0.0138

AC XY:

1026

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00344

Gnomad4 AMR

AF:

0.0106

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.0248

Gnomad4 SAS

AF:

0.00518

Gnomad4 FIN

AF:

0.0323

Gnomad4 NFE

AF:

0.0177

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.0131

Hom.:

Bravo

AF:

0.0118

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 20, 2019	- -
Likely 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	- -
Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.29

DANN

Benign

0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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