chr1-99880788-C-T

Variant summary

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

The NM_000642.3(AGL):​c.1892C>T​(p.Pro631Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,652 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. P631R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

AGL
NM_000642.3 missense

Scores

7
7
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.80
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, 0.775

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
AGLNM_000642.3 linkc.1892C>T p.Pro631Leu 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 linkc.1892C>T p.Pro631Leu missense_variant 14/341 NM_000642.3 ENSP00000355106.3 P35573-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461652
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727134
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.29
BayesDel_addAF
Pathogenic
0.39
D
BayesDel_noAF
Pathogenic
0.32
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.53
D;D;D;D;.
Eigen
Uncertain
0.63
Eigen_PC
Pathogenic
0.67
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.95
D;.;.;.;D
M_CAP
Benign
0.059
D
MetaRNN
Pathogenic
0.78
D;D;D;D;D
MetaSVM
Uncertain
0.20
D
MutationAssessor
Uncertain
2.4
M;M;M;M;.
PrimateAI
Uncertain
0.79
T
PROVEAN
Pathogenic
-7.3
D;D;D;D;D
REVEL
Pathogenic
0.67
Sift
Benign
0.052
T;T;T;T;T
Sift4G
Benign
0.11
T;T;T;T;T
Polyphen
0.71
P;P;P;P;P
Vest4
0.64
MutPred
0.80
Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);.;
MVP
0.93
MPC
0.050
ClinPred
0.79
D
GERP RS
6.1
Varity_R
0.54
gMVP
0.85

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs1553186376; hg19: chr1-100346344; API