NM_000642.3:c.25A>C

Variant names:

• chr1-99851067-A-C
• NM_000642.3:c.25A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000642.3(AGL):​c.25A>C​(p.Ile9Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign 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. I9V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: AGL NM_000642.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.87

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1862956).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGL	NM_000642.3	c.25A>C	p.Ile9Leu	missense_variant	Exon 2 of 34	ENST00000361915.8	NP_000633.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGL	ENST00000361915.8	c.25A>C	p.Ile9Leu	missense_variant	Exon 2 of 34	1	NM_000642.3	ENSP00000355106.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.072	T;T;T;T
Eigen	Benign	-0.13
Eigen_PC	Benign	0.073
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.76	T;.;.;.
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.19	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.90	L;L;L;L
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.1	N;N;N;N
REVEL	Benign	0.13
Sift	Benign	0.13	T;T;T;T
Sift4G	Benign	0.17	T;T;T;T
Polyphen		0.0010	B;B;B;B
Vest4		0.37
MutPred		0.35		Gain of disorder (P = 0.0523);Gain of disorder (P = 0.0523);Gain of disorder (P = 0.0523);Gain of disorder (P = 0.0523);
MVP		0.63
MPC		0.041
ClinPred		0.72	D
GERP RS		5.3
Varity_R		0.12
gMVP		0.40

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: chr1-100316623;