chr1-99870507-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000642.3(AGL):​c.772T>C​(p.Ser258Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

AGL
NM_000642.3 missense

Scores

1
12
6

Clinical Significance

Uncertain significance criteria provided, single submitter P:1U:1

Conservation

PhyloP100: 4.52
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AGLNM_000642.3 linkuse as main transcriptc.772T>C p.Ser258Pro missense_variant 6/34 ENST00000361915.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AGLENST00000361915.8 linkuse as main transcriptc.772T>C p.Ser258Pro missense_variant 6/341 NM_000642.3 P1P35573-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Pathogenic:1Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Glycogen storage disease type III Pathogenic:1Uncertain:1
Uncertain significance, criteria provided, single submittercurationDepartment Of Genetics, Sultan Qaboos University Hospital, Sultan Qaboos UniversityDec 30, 2017- -
Likely pathogenic, no assertion criteria providedclinical testingBioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.94
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
-0.020
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.43
T;T;T;T;.
Eigen
Uncertain
0.34
Eigen_PC
Uncertain
0.32
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Benign
0.84
T;.;.;.;T
M_CAP
Benign
0.064
D
MetaRNN
Uncertain
0.71
D;D;D;D;D
MetaSVM
Uncertain
0.071
D
MutationAssessor
Uncertain
2.5
M;M;M;M;.
MutationTaster
Benign
0.98
D;D;D;D;D;D;D
PrimateAI
Benign
0.41
T
PROVEAN
Uncertain
-2.8
D;D;D;D;D
REVEL
Uncertain
0.64
Sift
Benign
0.082
T;T;T;T;T
Sift4G
Benign
0.069
T;T;T;T;T
Polyphen
0.77
P;P;P;P;P
Vest4
0.57
MutPred
0.57
Gain of catalytic residue at S258 (P = 0.0035);Gain of catalytic residue at S258 (P = 0.0035);Gain of catalytic residue at S258 (P = 0.0035);Gain of catalytic residue at S258 (P = 0.0035);.;
MVP
0.92
MPC
0.18
ClinPred
0.97
D
GERP RS
3.0
Varity_R
0.61
gMVP
0.93

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs886039873; hg19: chr1-100336063; API