3-184248747-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_005787.6(ALG3):​c.194C>A​(p.Ala65Glu) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,098,276 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 9.1e-7 ( 0 hom. )

Consequence

ALG3
NM_005787.6 missense, splice_region

Scores

2
10
7
Splicing: ADA: 0.9918
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.23
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ALG3NM_005787.6 linkc.194C>A p.Ala65Glu missense_variant, splice_region_variant Exon 1 of 9 ENST00000397676.8 NP_005778.1 Q92685-1
ALG3NM_001006941.2 linkc.52+479C>A intron_variant Intron 1 of 8 NP_001006942.1 Q92685-2
ALG3NR_024533.1 linkn.225C>A splice_region_variant, non_coding_transcript_exon_variant Exon 1 of 8
ALG3NR_024534.1 linkn.190+35C>A intron_variant Intron 1 of 8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ALG3ENST00000397676.8 linkc.194C>A p.Ala65Glu missense_variant, splice_region_variant Exon 1 of 9 1 NM_005787.6 ENSP00000380793.3 Q92685-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
9.11e-7
AC:
1
AN:
1098276
Hom.:
0
Cov.:
35
AF XY:
0.00
AC XY:
0
AN XY:
542806
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000118
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.20
BayesDel_addAF
Pathogenic
0.27
D
BayesDel_noAF
Pathogenic
0.15
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.34
T
Eigen
Uncertain
0.20
Eigen_PC
Uncertain
0.37
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.95
D
M_CAP
Benign
0.075
D
MetaRNN
Uncertain
0.69
D
MetaSVM
Uncertain
-0.052
T
MutationAssessor
Benign
1.9
L
PrimateAI
Uncertain
0.71
T
PROVEAN
Benign
-0.13
N
REVEL
Uncertain
0.53
Sift
Uncertain
0.018
D
Sift4G
Benign
0.10
T
Polyphen
0.015
B
Vest4
0.66
MutPred
0.54
Loss of catalytic residue at Y66 (P = 0.1017);
MVP
0.95
MPC
0.14
ClinPred
0.93
D
GERP RS
5.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.71
gMVP
0.90

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
0.99
dbscSNV1_RF
Pathogenic
0.95
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-183966535; API