rs706584

Variant names:

• chr3-184242464-A-C
• rs706584
• NM_005787.6:c.*50T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.158
• Publications: 16 publications found

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]

VWA5B2 (HGNC:25144): (von Willebrand factor A domain containing 5B2)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005787.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG3	NM_005787.6	MANE Select	c.*50T>G		3_prime_UTR	Exon 9 of 9	NP_005778.1	Q92685-1
	ALG3	NM_001006941.2		c.*50T>G		3_prime_UTR	Exon 9 of 9	NP_001006942.1	Q92685-2
	ALG3	NR_024533.1		n.1298T>G		non_coding_transcript_exon	Exon 8 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG3	ENST00000397676.8	TSL:1 MANE Select	c.*50T>G		3_prime_UTR	Exon 9 of 9	ENSP00000380793.3	Q92685-1
	ALG3	ENST00000445626.6	TSL:1	c.*50T>G		3_prime_UTR	Exon 9 of 9	ENSP00000402744.2	Q92685-2
	ALG3	ENST00000411922.5	TSL:1	n.*943T>G		non_coding_transcript_exon	Exon 8 of 8	ENSP00000394917.1	F8WE30

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35965 AN: 151998 Hom.: 4365 Cov.: 32

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

GnomAD2 exomes AF: 0.210 AC: 44719 AN: 213090 AF XY: 0.210

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 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.: 31 AF XY: 0.223 AC XY: 159129 AN XY: 712494

African (AFR) AF: 0.292 AC: 9703 AN: 33210

American (AMR) AF: 0.169 AC: 6730 AN: 39786

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 4352 AN: 25646

East Asian (EAS) AF: 0.166 AC: 6496 AN: 39050

South Asian (SAS) AF: 0.224 AC: 18597 AN: 82906

European-Finnish (FIN) AF: 0.190 AC: 9924 AN: 52154

Middle Eastern (MID) AF: 0.232 AC: 1256 AN: 5422

European-Non Finnish (NFE) AF: 0.229 AC: 251688 AN: 1098902

Other (OTH) AF: 0.221 AC: 13164 AN: 59608

GnomAD4 genome AF: 0.237 AC: 35991 AN: 152118 Hom.: 4372 Cov.: 32 AF XY: 0.232 AC XY: 17250 AN XY: 74362

African (AFR) AF: 0.291 AC: 12067 AN: 41464

American (AMR) AF: 0.213 AC: 3258 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 567 AN: 3466

East Asian (EAS) AF: 0.189 AC: 977 AN: 5164

South Asian (SAS) AF: 0.226 AC: 1090 AN: 4824

European-Finnish (FIN) AF: 0.195 AC: 2064 AN: 10610

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15262 AN: 67984

Other (OTH) AF: 0.237 AC: 500 AN: 2112

Alfa AF: 0.227 Hom.: 1869

Bravo AF: 0.239

Asia WGS AF: 0.235 AC: 822 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	ALG3-congenital disorder of glycosylation (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.8
DANN	Benign	0.45
PhyloP100		0.16
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs706584; hg19: chr3-183960252; COSMIC: COSV56611079; COSMIC: COSV56611079;