rs766053670

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_013338.5(ALG5):​c.770G>T​(p.Arg257Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,718 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R257Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ALG5
NM_013338.5 missense

Scores

9
8
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.82
Variant links:
Genes affected
ALG5 (HGNC:20266): (ALG5 dolichyl-phosphate beta-glucosyltransferase) This gene encodes a member of the glycosyltransferase 2 family. The encoded protein participates in glucosylation of the oligomannose core in N-linked glycosylation of proteins. The addition of glucose residues to the oligomannose core is necessary to ensure substrate recognition, and therefore, effectual transfer of the oligomannose core to the nascent glycoproteins. 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 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.883

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ALG5NM_013338.5 linkc.770G>T p.Arg257Leu missense_variant Exon 8 of 10 ENST00000239891.4 NP_037470.1 Q9Y673-1
ALG5NM_001142364.1 linkc.680G>T p.Arg227Leu missense_variant Exon 7 of 9 NP_001135836.1 Q9Y673-2
ALG5XM_047430283.1 linkc.581G>T p.Arg194Leu missense_variant Exon 6 of 8 XP_047286239.1
ALG5XR_007063678.1 linkn.946G>T non_coding_transcript_exon_variant Exon 9 of 9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ALG5ENST00000239891.4 linkc.770G>T p.Arg257Leu missense_variant Exon 8 of 10 1 NM_013338.5 ENSP00000239891.3 Q9Y673-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460718
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
726706
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:
9.00e-7
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
Pathogenic
0.85
BayesDel_addAF
Pathogenic
0.36
D
BayesDel_noAF
Pathogenic
0.29
CADD
Pathogenic
30
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.63
.;D
Eigen
Pathogenic
1.0
Eigen_PC
Pathogenic
0.95
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.97
D;D
M_CAP
Benign
0.064
D
MetaRNN
Pathogenic
0.88
D;D
MetaSVM
Uncertain
0.11
D
MutationAssessor
Pathogenic
3.8
.;H
PrimateAI
Uncertain
0.67
T
PROVEAN
Pathogenic
-6.8
D;D
REVEL
Uncertain
0.59
Sift
Uncertain
0.0030
D;D
Sift4G
Uncertain
0.0040
D;D
Polyphen
1.0
D;D
Vest4
0.94
MutPred
0.57
.;Gain of catalytic residue at W258 (P = 0);
MVP
0.91
MPC
1.2
ClinPred
1.0
D
GERP RS
5.7
Varity_R
0.74
gMVP
0.93

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: chr13-37539715; API