1-99881378-C-A

Variant names:

• chr1-99881378-C-A
• NM_000642.3:c.2088C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000642.3(AGL):​c.2088C>A​(p.Ser696Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S696S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: AGL NM_000642.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.292

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2734015).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGL	NM_000642.3	c.2088C>A	p.Ser696Arg	missense_variant	Exon 16 of 34	ENST00000361915.8	NP_000633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGL	ENST00000361915.8	c.2088C>A	p.Ser696Arg	missense_variant	Exon 16 of 34	1	NM_000642.3	ENSP00000355106.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461804 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727200

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	7.6
DANN	Uncertain	0.98
DEOGEN2	Benign	0.18	T;T;T;T;.
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.44	N
LIST_S2	Uncertain	0.96	D;.;.;.;D
M_CAP	Uncertain	0.085	D
MetaRNN	Benign	0.27	T;T;T;T;T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.8	L;L;L;L;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.0	N;N;N;N;N
REVEL	Uncertain	0.43
Sift	Benign	0.073	T;T;T;T;T
Sift4G	Benign	0.096	T;T;T;T;T
Polyphen		0.13	B;B;B;B;B
Vest4		0.45
MutPred		0.54		Loss of glycosylation at S696 (P = 0.003);Loss of glycosylation at S696 (P = 0.003);Loss of glycosylation at S696 (P = 0.003);Loss of glycosylation at S696 (P = 0.003);.;
MVP		0.82
MPC		0.051
ClinPred		0.85	D
GERP RS		0.66
Varity_R		0.20
gMVP		0.67

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-100346934;