chr11-78101085-T-C
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_024079.5(ALG8):c.1460A>G(p.Tyr487Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000167 in 1,613,964 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00018 ( 1 hom. )
Consequence
ALG8
NM_024079.5 missense
NM_024079.5 missense
Scores
1
12
6
Clinical Significance
Conservation
PhyloP100: 2.75
Genes affected
ALG8 (HGNC:23161): (ALG8 alpha-1,3-glucosyltransferase) This gene encodes a member of the ALG6/ALG8 glucosyltransferase family. The encoded protein catalyzes the addition of the second glucose residue to the lipid-linked oligosaccharide precursor for N-linked glycosylation of proteins. Mutations in this gene have been associated with congenital disorder of glycosylation type Ih (CDG-Ih). Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.11508578).
BP6
?
Variant 11-78101085-T-C is Benign according to our data. Variant chr11-78101085-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 306211.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALG8 | NM_024079.5 | c.1460A>G | p.Tyr487Cys | missense_variant | 13/13 | ENST00000299626.10 | |
ALG8 | XM_005274247.4 | c.1433A>G | p.Tyr478Cys | missense_variant | 13/13 | ||
ALG8 | NM_001007027.3 | c.*131A>G | 3_prime_UTR_variant | 14/14 | |||
ALG8 | XR_950044.4 | n.1358A>G | non_coding_transcript_exon_variant | 12/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALG8 | ENST00000299626.10 | c.1460A>G | p.Tyr487Cys | missense_variant | 13/13 | 1 | NM_024079.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152122Hom.: 0 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
6
AN:
152122
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000302 AC: 76AN: 251354Hom.: 0 AF XY: 0.000398 AC XY: 54AN XY: 135836
GnomAD3 exomes
AF:
AC:
76
AN:
251354
Hom.:
AF XY:
AC XY:
54
AN XY:
135836
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000180 AC: 263AN: 1461724Hom.: 1 Cov.: 33 AF XY: 0.000265 AC XY: 193AN XY: 727176
GnomAD4 exome
AF:
AC:
263
AN:
1461724
Hom.:
Cov.:
33
AF XY:
AC XY:
193
AN XY:
727176
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152240Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74446
GnomAD4 genome
?
AF:
AC:
6
AN:
152240
Hom.:
Cov.:
33
AF XY:
AC XY:
3
AN XY:
74446
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
?
AF:
AC:
38
Asia WGS
AF:
AC:
3
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
ALG8 congenital disorder of glycosylation Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jul 29, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
ALG8 congenital disorder of glycosylation;C4693472:Polycystic liver disease 3 with or without kidney cysts Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 15, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Uncertain
D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Pathogenic
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
P;.
Vest4
MutPred
Gain of helix (P = 0.0496);.;
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at