3-184242568-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_ModeratePM2PP5

The NM_005787.6(ALG3):​c.1263G>A​(p.Trp421*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)

Consequence

ALG3
NM_005787.6 stop_gained

Scores

5
1
1

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.87
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]
VWA5B2 (HGNC:25144): (von Willebrand factor A domain containing 5B2)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.041 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 3-184242568-C-T is Pathogenic according to our data. Variant chr3-184242568-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 617476.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ALG3NM_005787.6 linkc.1263G>A p.Trp421* stop_gained Exon 9 of 9 ENST00000397676.8 NP_005778.1 Q92685-1
VWA5B2NM_001390846.1 linkc.*530C>T downstream_gene_variant ENST00000691901.1 NP_001377775.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ALG3ENST00000397676.8 linkc.1263G>A p.Trp421* stop_gained Exon 9 of 9 1 NM_005787.6 ENSP00000380793.3 Q92685-1
VWA5B2ENST00000691901.1 linkc.*530C>T downstream_gene_variant NM_001390846.1 ENSP00000509115.1 Q8N398

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

ALG3-congenital disorder of glycosylation Pathogenic:1
-
Lab Thiel (Congenital Disorders of Glycosylation), Center for Child and Adolescent Medicine
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.58
D
BayesDel_noAF
Pathogenic
0.60
CADD
Pathogenic
40
DANN
Uncertain
0.99
Eigen
Pathogenic
0.93
Eigen_PC
Pathogenic
0.81
FATHMM_MKL
Pathogenic
0.97
D
Vest4
0.80
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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.

Other links and lift over

dbSNP: rs1560161567; hg19: chr3-183960356; API