rs706584

Variant summary

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

The NM_005787.6(ALG3):c.*50T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 1,588,802 control chromosomes in the GnomAD database, including 41,130 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4372 hom., cov: 32)

Exomes 𝑓: 0.22 ( 36758 hom. )

Consequence

ALG3
NM_005787.6 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.158

Variant links:

Genes affected

ALG3 (HGNC:23056): (ALG3 alpha-1,3- mannosyltransferase) This gene encodes a member of the ALG3 family. The encoded protein catalyses the addition of the first dol-P-Man derived mannose in an alpha 1,3 linkage to Man5GlcNAc2-PP-Dol. Defects in this gene have been associated with congenital disorder of glycosylation type Id (CDG-Id) characterized by abnormal N-glycosylation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2008]

ALG3 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=-0.89).

BP6

Variant 3-184242464-A-C is Benign according to our data. Variant chr3-184242464-A-C is described in ClinVar as [Benign]. Clinvar id is 259884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
ALG3	NM_005787.6 linkuse as main transcript	c.*50T>G	3_prime_UTR_variant	9/9	ENST00000397676.8
ALG3	NM_001006941.2 linkuse as main transcript	c.*50T>G	3_prime_UTR_variant	9/9
ALG3	NR_024533.1 linkuse as main transcript	n.1298T>G	non_coding_transcript_exon_variant	8/8
ALG3	NR_024534.1 linkuse as main transcript	n.1361T>G	non_coding_transcript_exon_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALG3	ENST00000397676.8 linkuse as main transcript	c.*50T>G		3_prime_UTR_variant	9/9	1	NM_005787.6	P1	Q92685-1

Frequencies

GnomAD3 genomes

AF:

0.237

AC:

35965

AN:

151998

Hom.:

4365

Cov.:

show subpopulations

Gnomad AFR

AF:

0.291

Gnomad AMI

AF:

0.157

Gnomad AMR

AF:

0.213

Gnomad ASJ

AF:

0.164

Gnomad EAS

AF:

0.190

Gnomad SAS

AF:

0.227

Gnomad FIN

AF:

0.195

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.225

Gnomad OTH

AF:

0.239

GnomAD3 exomes

AF:

0.210

AC:

44719

AN:

213090

Hom.:

4840

AF XY:

0.210

AC XY:

24156

AN XY:

115010

show subpopulations

Gnomad AFR exome

AF:

0.283

Gnomad AMR exome

AF:

0.162

Gnomad ASJ exome

AF:

0.168

Gnomad EAS exome

AF:

0.188

Gnomad SAS exome

AF:

0.225

Gnomad FIN exome

AF:

0.191

Gnomad NFE exome

AF:

0.222

Gnomad OTH exome

AF:

0.208

GnomAD4 exome

AF:

0.224

AC:

321910

AN:

1436684

Hom.:

36758

Cov.:

AF XY:

0.223

AC XY:

159129

AN XY:

712494

show subpopulations

Gnomad4 AFR exome

AF:

0.292

Gnomad4 AMR exome

AF:

0.169

Gnomad4 ASJ exome

AF:

0.170

Gnomad4 EAS exome

AF:

0.166

Gnomad4 SAS exome

AF:

0.224

Gnomad4 FIN exome

AF:

0.190

Gnomad4 NFE exome

AF:

0.229

Gnomad4 OTH exome

AF:

0.221

GnomAD4 genome

AF:

0.237

AC:

35991

AN:

152118

Hom.:

4372

Cov.:

AF XY:

0.232

AC XY:

17250

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.291

Gnomad4 AMR

AF:

0.213

Gnomad4 ASJ

AF:

0.164

Gnomad4 EAS

AF:

0.189

Gnomad4 SAS

AF:

0.226

Gnomad4 FIN

AF:

0.195

Gnomad4 NFE

AF:

0.224

Gnomad4 OTH

AF:

0.237

Alfa

AF:

0.225

Hom.:

1526

Bravo

AF:

0.239

Asia WGS

AF:

0.235

AC:

822

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

- -

ALG3-congenital disorder of glycosylation

Benign:1

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

BayesDel_noAF

Benign

-0.89

Cadd

Benign

3.8

Dann

Benign

0.45

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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