Variant rs4075331 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.768+42T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 1,586,880 control chromosomes in the GnomAD database, including 59,250 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 13926 hom., cov: 33)

Exomes 𝑓: 0.23 ( 45324 hom. )

Consequence

ALG12
NM_024105.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.16

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=-1.0).

BP6

Variant 22-49909202-A-G is Benign according to our data. Variant chr22-49909202-A-G is described in ClinVar as [Benign]. Clinvar id is 261688.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
ALG12	NM_024105.4 link	c.768+42T>C	intron_variant	ENST00000330817.11	NP_077010.1	Q9BV10A0A024R4V6
ALG12	XM_017028936.2 link	c.768+42T>C	intron_variant		XP_016884425.1
ALG12	XM_017028937.2 link	c.768+42T>C	intron_variant		XP_016884426.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALG12	ENST00000330817.11 link	c.768+42T>C		intron_variant		1	NM_024105.4	ENSP00000333813.5		Q9BV10
ALG12	ENST00000492791.1 link	n.297+42T>C		intron_variant		3		ENSP00000417387.1		H7C4I6

Frequencies

GnomAD3 genomes

AF:

0.358

AC:

54361

AN:

152008

Hom.:

13867

Cov.:

show subpopulations

Gnomad AFR

AF:

0.729

Gnomad AMI

AF:

0.467

Gnomad AMR

AF:

0.223

Gnomad ASJ

AF:

0.304

Gnomad EAS

AF:

0.145

Gnomad SAS

AF:

0.413

Gnomad FIN

AF:

0.166

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.207

Gnomad OTH

AF:

0.306

GnomAD3 exomes

AF:

0.256

AC:

64121

AN:

250590

Hom.:

11250

AF XY:

0.259

AC XY:

35050

AN XY:

135532

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:

0.428

Gnomad FIN exome

AF:

0.166

Gnomad NFE exome

AF:

0.205

Gnomad OTH exome

AF:

0.233

GnomAD4 exome

AF:

0.230

AC:

329325

AN:

1434754

Hom.:

45324

Cov.:

AF XY:

0.235

AC XY:

168042

AN XY:

715472

show subpopulations

Gnomad4 AFR exome

AF:

0.753

Gnomad4 AMR exome

AF:

0.160

Gnomad4 ASJ exome

AF:

0.298

Gnomad4 EAS exome

AF:

0.137

Gnomad4 SAS exome

AF:

0.427

Gnomad4 FIN exome

AF:

0.169

Gnomad4 NFE exome

AF:

0.204

Gnomad4 OTH exome

AF:

0.257

GnomAD4 genome

AF:

0.358

AC:

54475

AN:

152126

Hom.:

13926

Cov.:

AF XY:

0.353

AC XY:

26291

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.729

Gnomad4 AMR

AF:

0.223

Gnomad4 ASJ

AF:

0.304

Gnomad4 EAS

AF:

0.145

Gnomad4 SAS

AF:

0.412

Gnomad4 FIN

AF:

0.166

Gnomad4 NFE

AF:

0.207

Gnomad4 OTH

AF:

0.310

Alfa

AF:

0.287

Hom.:

1571

Bravo

AF:

0.370

Asia WGS

AF:

0.335

AC:

1168

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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	-	- -

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

-1.0

CADD

Benign

0.069

DANN

Benign

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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