chr15-42327398-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_198141.3(GANC):c.1456G>A(p.Val486Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,461,104 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
GANC
NM_198141.3 missense
NM_198141.3 missense
Scores
1
10
8
Clinical Significance
Conservation
PhyloP100: 5.62
Genes affected
GANC (HGNC:4139): (glucosidase alpha, neutral C) Glycosyl hydrolase enzymes hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. This gene encodes a member of glycosyl hydrolases family 31. This enzyme hydrolyses terminal, non-reducing 1,4-linked alpha-D-glucose residues and releases alpha-D-glucose. This is a key enzyme in glycogen metabolism and its gene localizes to a chromosomal region (15q15) that is associated with susceptibility to diabetes. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2014]
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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 |
---|---|---|---|---|---|---|---|
GANC | NM_198141.3 | c.1456G>A | p.Val486Ile | missense_variant | 13/24 | ENST00000318010.13 | |
GANC | NM_001393928.1 | c.1456G>A | p.Val486Ile | missense_variant | 14/25 | ||
GANC | NM_001393929.1 | c.1456G>A | p.Val486Ile | missense_variant | 14/25 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GANC | ENST00000318010.13 | c.1456G>A | p.Val486Ile | missense_variant | 13/24 | 1 | NM_198141.3 | P1 | |
GANC | ENST00000567421.1 | n.1429G>A | non_coding_transcript_exon_variant | 12/12 | 5 | ||||
GANC | ENST00000568953.1 | n.160G>A | non_coding_transcript_exon_variant | 2/3 | 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250688Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135472
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GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461104Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4AN XY: 726830
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 08, 2023 | The c.1456G>A (p.V486I) alteration is located in exon 13 (coding exon 13) of the GANC gene. This alteration results from a G to A substitution at nucleotide position 1456, causing the valine (V) at amino acid position 486 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
T
MetaSVM
Pathogenic
D
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
P
Vest4
MutPred
Loss of methylation at K485 (P = 0.0631);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: 44
Find out detailed SpliceAI scores and Pangolin per-transcript scores at