11-62625885-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_198334.3(GANAB):​c.2765A>G​(p.Glu922Gly) 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

GANAB
NM_198334.3 missense

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.23
Variant links:
Genes affected
GANAB (HGNC:4138): (glucosidase II alpha subunit) This gene encodes the alpha subunit of glucosidase II and a member of the glycosyl hydrolase 31 family of proteins. The heterodimeric enzyme glucosidase II plays a role in protein folding and quality control by cleaving glucose residues from immature glycoproteins in the endoplasmic reticulum. Expression of the encoded protein is elevated in lung tumor tissue and in response to UV irradiation. Mutations in this gene cause autosomal-dominant polycystic kidney and liver disease. [provided by RefSeq, Jul 2016]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), GANAB. . Gene score misZ 2.2404 (greater than the threshold 3.09). Trascript score misZ 3.2543 (greater than threshold 3.09). GenCC has associacion of gene with polycystic kidney disease 3 with or without polycystic liver disease, autosomal dominant polycystic kidney disease.
BP4
Computational evidence support a benign effect (MetaRNN=0.2329664).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GANABNM_198334.3 linkuse as main transcriptc.2765A>G p.Glu922Gly missense_variant 24/24 ENST00000356638.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GANABENST00000356638.8 linkuse as main transcriptc.2765A>G p.Glu922Gly missense_variant 24/241 NM_198334.3 P1Q14697-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJul 01, 2024GANAB: PM2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Uncertain
0.064
T
BayesDel_noAF
Benign
-0.15
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.10
.;.;.;T;.
Eigen
Benign
-0.12
Eigen_PC
Benign
0.048
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.85
D;D;.;D;D
M_CAP
Uncertain
0.093
D
MetaRNN
Benign
0.23
T;T;T;T;T
MetaSVM
Uncertain
-0.042
T
MutationAssessor
Benign
0.99
.;.;.;L;.
MutationTaster
Benign
0.79
D;D;D;D
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-1.6
N;N;.;N;N
REVEL
Uncertain
0.30
Sift
Benign
0.080
T;T;.;T;T
Sift4G
Benign
0.32
T;T;.;T;T
Polyphen
0.0020
B;.;.;B;B
Vest4
0.22
MutPred
0.37
.;.;.;Loss of solvent accessibility (P = 0.0769);.;
MVP
0.42
MPC
0.31
ClinPred
0.58
D
GERP RS
4.8
Varity_R
0.16
gMVP
0.37

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: chr11-62393357; API