rs376460143

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_198334.3(GANAB):​c.2512-13A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000127 in 1,580,384 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000063 ( 0 hom. )

Consequence

GANAB
NM_198334.3 intron

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0450

Publications

0 publications found
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]
GANAB Gene-Disease associations (from GenCC):
  • polycystic kidney disease 3 with or without polycystic liver disease
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
  • autosomal dominant polycystic kidney disease
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 11-62626460-T-C is Benign according to our data. Variant chr11-62626460-T-C is described in CliVar as Likely_benign. Clinvar id is 1644852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62626460-T-C is described in CliVar as Likely_benign. Clinvar id is 1644852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62626460-T-C is described in CliVar as Likely_benign. Clinvar id is 1644852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62626460-T-C is described in CliVar as Likely_benign. Clinvar id is 1644852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62626460-T-C is described in CliVar as Likely_benign. Clinvar id is 1644852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62626460-T-C is described in CliVar as Likely_benign. Clinvar id is 1644852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62626460-T-C is described in CliVar as Likely_benign. Clinvar id is 1644852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62626460-T-C is described in CliVar as Likely_benign. Clinvar id is 1644852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62626460-T-C is described in CliVar as Likely_benign. Clinvar id is 1644852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62626460-T-C is described in CliVar as Likely_benign. Clinvar id is 1644852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62626460-T-C is described in CliVar as Likely_benign. Clinvar id is 1644852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62626460-T-C is described in CliVar as Likely_benign. Clinvar id is 1644852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62626460-T-C is described in CliVar as Likely_benign. Clinvar id is 1644852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62626460-T-C is described in CliVar as Likely_benign. Clinvar id is 1644852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62626460-T-C is described in CliVar as Likely_benign. Clinvar id is 1644852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62626460-T-C is described in CliVar as Likely_benign. Clinvar id is 1644852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62626460-T-C is described in CliVar as Likely_benign. Clinvar id is 1644852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62626460-T-C is described in CliVar as Likely_benign. Clinvar id is 1644852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62626460-T-C is described in CliVar as Likely_benign. Clinvar id is 1644852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62626460-T-C is described in CliVar as Likely_benign. Clinvar id is 1644852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62626460-T-C is described in CliVar as Likely_benign. Clinvar id is 1644852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62626460-T-C is described in CliVar as Likely_benign. Clinvar id is 1644852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62626460-T-C is described in CliVar as Likely_benign. Clinvar id is 1644852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GANABNM_198334.3 linkc.2512-13A>G intron_variant Intron 21 of 23 ENST00000356638.8 NP_938148.1 Q14697-1V9HWJ0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GANABENST00000356638.8 linkc.2512-13A>G intron_variant Intron 21 of 23 1 NM_198334.3 ENSP00000349053.3 Q14697-1

Frequencies

GnomAD3 genomes
AF:
0.0000461
AC:
7
AN:
151970
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000169
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000199
AC:
5
AN:
251412
AF XY:
0.0000221
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.00000630
AC:
9
AN:
1428296
Hom.:
0
Cov.:
25
AF XY:
0.00000702
AC XY:
5
AN XY:
712454
show subpopulations
African (AFR)
AF:
0.000214
AC:
7
AN:
32734
American (AMR)
AF:
0.00
AC:
0
AN:
44686
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25930
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39550
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85580
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53404
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5702
European-Non Finnish (NFE)
AF:
9.25e-7
AC:
1
AN:
1081450
Other (OTH)
AF:
0.0000169
AC:
1
AN:
59260
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.519
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000723
AC:
11
AN:
152088
Hom.:
0
Cov.:
32
AF XY:
0.0000673
AC XY:
5
AN XY:
74312
show subpopulations
African (AFR)
AF:
0.000265
AC:
11
AN:
41486
American (AMR)
AF:
0.00
AC:
0
AN:
15278
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3466
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5184
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4802
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10572
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
67980
Other (OTH)
AF:
0.00
AC:
0
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.554
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.0000945

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:1
Nov 29, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Polycystic kidney disease 3 with or without polycystic liver disease Benign:1
Oct 25, 2021
Fulgent Genetics, Fulgent Genetics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
1.8
DANN
Benign
0.48
PhyloP100
-0.045
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs376460143; hg19: chr11-62393932; API