dbSNP rs573414976: ALG3:p.Ala414Ala (chr3-184242589-G-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_ModerateBP6_ModerateBP7

The NM_005787.6(ALG3):c.1242C>T(p.Ala414Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000176 in 1,604,308 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00018 ( 1 hom. )

Consequence

ALG3
NM_005787.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.629

Publications

0 publications found

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:

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

VWA5B2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.114).

BP6

Variant 3-184242589-G-A is Benign according to our data. Variant chr3-184242589-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2741581.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.629 with no splicing effect.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ALG3	NM_005787.6	MANE Select	c.1242C>T	p.Ala414Ala	synonymous	Exon 9 of 9	NP_005778.1	Q92685-1
ALG3	NM_001006941.2		c.1098C>T	p.Ala366Ala	synonymous	Exon 9 of 9	NP_001006942.1	Q92685-2
ALG3	NR_024533.1		n.1173C>T		non_coding_transcript_exon	Exon 8 of 8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ALG3	ENST00000397676.8	TSL:1 MANE Select	c.1242C>T	p.Ala414Ala	synonymous	Exon 9 of 9	ENSP00000380793.3	Q92685-1
ALG3	ENST00000445626.6	TSL:1	c.1098C>T	p.Ala366Ala	synonymous	Exon 9 of 9	ENSP00000402744.2	Q92685-2
ALG3	ENST00000411922.5	TSL:1	n.*818C>T		non_coding_transcript_exon	Exon 8 of 8	ENSP00000394917.1	F8WE30

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000245

AC:

AN:

240634

AF XY:

0.000215

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000587

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000279

Gnomad FIN exome

AF:

0.00171

Gnomad NFE exome

AF:

0.0000741

Gnomad OTH exome

AF:

0.000512

GnomAD4 exome

AF:

0.000182

AC:

265

AN:

1452092

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

126

AN XY:

720862

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33318

American (AMR)

AF:

0.0000451

AC:

AN:

44378

Ashkenazi Jewish (ASJ)

AF:

0.0000391

AC:

AN:

25556

East Asian (EAS)

AF:

0.000455

AC:

AN:

39526

South Asian (SAS)

AF:

0.000211

AC:

AN:

85190

European-Finnish (FIN)

AF:

0.00149

AC:

AN:

53082

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5714

European-Non Finnish (NFE)

AF:

0.000128

AC:

141

AN:

1105360

Other (OTH)

AF:

0.0000834

AC:

AN:

59968

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000118

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41454

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.000207

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00122

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000604

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

ALG3-congenital disorder of glycosylation (1)

ALG3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

1.4

(source)

DANN

Benign

0.74

PhyloP100

-0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over