rs139488862

Variant summary

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

The NM_000642.3(AGL):​c.1759C>A​(p.His587Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. H587Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

AGL
NM_000642.3 missense

Scores

4
12
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.51
Variant links:
Genes affected
AGL (HGNC:321): (amylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase) This gene encodes the glycogen debrancher enzyme which is involved in glycogen degradation. This enzyme has two independent catalytic activities which occur at different sites on the protein: a 4-alpha-glucotransferase activity and a amylo-1,6-glucosidase activity. Mutations in this gene are associated with glycogen storage disease although a wide range of enzymatic and clinical variability occurs which may be due to tissue-specific alternative splicing. Alternatively spliced transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 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
MetaRNN computational evidence supports a deleterious effect, 0.798

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
AGLNM_000642.3 linkuse as main transcriptc.1759C>A p.His587Asn missense_variant 14/34 ENST00000361915.8 NP_000633.2 P35573-1A0A0S2A4E4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
AGLENST00000361915.8 linkuse as main transcriptc.1759C>A p.His587Asn missense_variant 14/341 NM_000642.3 ENSP00000355106.3 P35573-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.45
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
-0.020
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.36
T;T;T;T;.
Eigen
Pathogenic
0.70
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.96
D;.;.;.;D
M_CAP
Benign
0.079
D
MetaRNN
Pathogenic
0.80
D;D;D;D;D
MetaSVM
Uncertain
0.36
D
MutationAssessor
Uncertain
2.8
M;M;M;M;.
PrimateAI
Uncertain
0.71
T
PROVEAN
Pathogenic
-4.6
D;D;D;D;D
REVEL
Uncertain
0.48
Sift
Uncertain
0.016
D;D;D;D;D
Sift4G
Uncertain
0.059
T;T;T;T;D
Polyphen
1.0
D;D;D;D;D
Vest4
0.85
MutPred
0.23
Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);.;
MVP
0.96
MPC
0.15
ClinPred
0.99
D
GERP RS
5.8
Varity_R
0.53
gMVP
0.79

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
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: rs139488862; hg19: chr1-100346211; API