1-63370979-T-C
Variant names:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_ModeratePS1_ModeratePM2PP5_Moderate
The NM_013339.4(ALG6):āc.2T>Cā(p.Met1?) variant causes a start lost change. The variant allele was found at a frequency of 0.000005 in 1,598,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 32)
Exomes š: 0.0000048 ( 0 hom. )
Consequence
ALG6
NM_013339.4 start_lost
NM_013339.4 start_lost
Scores
7
6
3
Clinical Significance
Conservation
PhyloP100: 4.17
Genes affected
ALG6 (HGNC:23157): (ALG6 alpha-1,3-glucosyltransferase) This gene encodes a member of the ALG6/ALG8 glucosyltransferase family. The encoded protein catalyzes the addition of the first glucose residue to the growing lipid-linked oligosaccharide precursor of N-linked glycosylation. Mutations in this gene are associated with congenital disorders of glycosylation type Ic. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PVS1
Start lost variant, next in-frame start position is after 3 pathogenic variants. Next in-frame start position is after 7 codons. Genomic position: 63370996. Lost 0.012 part of the original CDS.
PS1
Another start lost variant in NM_013339.4 (ALG6) was described as [Conflicting_classifications_of_pathogenicity] in ClinVar as 554144
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 1-63370979-T-C is Pathogenic according to our data. Variant chr1-63370979-T-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 558047.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152122Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000484 AC: 7AN: 1446584Hom.: 0 Cov.: 28 AF XY: 0.00000694 AC XY: 5AN XY: 720712
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152122Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74302
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
ALG6-congenital disorder of glycosylation 1C Pathogenic:1
Apr 25, 2018
Counsyl
Significance: Likely pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Pathogenic
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Vest4
MutPred
Gain of catalytic residue at M1 (P = 0.0216);Gain of catalytic residue at M1 (P = 0.0216);
MVP
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at