chr3-184248927-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005787.6(ALG3):ā€‹c.14T>Gā€‹(p.Leu5Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000021 in 1,431,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

ALG3
NM_005787.6 missense

Scores

5
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.14
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10181606).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ALG3NM_005787.6 linkuse as main transcriptc.14T>G p.Leu5Arg missense_variant 1/9 ENST00000397676.8 NP_005778.1 Q92685-1
ALG3NM_001006941.2 linkuse as main transcriptc.52+299T>G intron_variant NP_001006942.1 Q92685-2
ALG3NR_024533.1 linkuse as main transcriptn.45T>G non_coding_transcript_exon_variant 1/8
ALG3NR_024534.1 linkuse as main transcriptn.45T>G non_coding_transcript_exon_variant 1/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ALG3ENST00000397676.8 linkuse as main transcriptc.14T>G p.Leu5Arg missense_variant 1/91 NM_005787.6 ENSP00000380793.3 Q92685-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000506
AC:
1
AN:
197636
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
109664
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000116
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000210
AC:
3
AN:
1431554
Hom.:
0
Cov.:
34
AF XY:
0.00000141
AC XY:
1
AN XY:
709350
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:
0.00000182
Gnomad4 OTH exome
AF:
0.0000169
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.067
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
-0.040
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Benign
0.079
T
Eigen
Benign
-0.55
Eigen_PC
Benign
-0.34
FATHMM_MKL
Benign
0.42
N
LIST_S2
Benign
0.72
T
M_CAP
Benign
0.077
D
MetaRNN
Benign
0.10
T
MetaSVM
Benign
-0.81
T
MutationAssessor
Benign
1.5
L
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
0.74
N
REVEL
Uncertain
0.31
Sift
Benign
0.88
T
Sift4G
Benign
0.83
T
Polyphen
0.013
B
Vest4
0.43
MVP
0.84
MPC
0.13
ClinPred
0.21
T
GERP RS
4.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.0
Varity_R
0.32
gMVP
0.54

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: rs878853028; hg19: chr3-183966715; API