11-62625819-C-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_198334.3(GANAB):c.2831G>C(p.Arg944Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000129 in 1,585,692 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R944Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

GANAB
NM_198334.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.668

Publications

2 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: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen
autosomal dominant polycystic kidney disease
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

GANAB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.35594058).

BS2

High AC in GnomAd4 at 15 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198334.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GANAB	NM_198334.3	MANE Select	c.2831G>C	p.Arg944Pro	missense	Exon 24 of 24	NP_938148.1	Q14697-1
GANAB	NM_198335.4		c.2897G>C	p.Arg966Pro	missense	Exon 25 of 25	NP_938149.2	Q14697-2
GANAB	NM_001278192.2		c.2555G>C	p.Arg852Pro	missense	Exon 22 of 22	NP_001265121.1	E9PKU7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GANAB	ENST00000356638.8	TSL:1 MANE Select	c.2831G>C	p.Arg944Pro	missense	Exon 24 of 24	ENSP00000349053.3	Q14697-1
GANAB	ENST00000346178.8	TSL:1	c.2897G>C	p.Arg966Pro	missense	Exon 25 of 25	ENSP00000340466.4	Q14697-2
GANAB	ENST00000540933.5	TSL:1	c.2540G>C	p.Arg847Pro	missense	Exon 23 of 23	ENSP00000442962.1	F5H6X6

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.000176

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000879

AC:

AN:

250334

AF XY:

0.0000739

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:

0.000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000132

AC:

189

AN:

1433570

Hom.:

Cov.:

AF XY:

0.000105

AC XY:

AN XY:

714730

show subpopulations

African (AFR)

AF:

0.0000304

AC:

AN:

32922

American (AMR)

AF:

0.00

AC:

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25976

East Asian (EAS)

AF:

0.00

AC:

AN:

39560

South Asian (SAS)

AF:

0.00

AC:

AN:

85746

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5358

European-Non Finnish (NFE)

AF:

0.000168

AC:

183

AN:

1086544

Other (OTH)

AF:

0.0000674

AC:

AN:

59362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000986

AC:

AN:

152122

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41410

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000176

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000226

Hom.:

Bravo

AF:

0.000140

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000115

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Benign

-0.0079

BayesDel_noAF

Uncertain

0.030

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.95

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.36

MetaSVM

Uncertain

0.32

MutationAssessor

Benign

0.81

PhyloP100

0.67

PrimateAI

Benign

0.34

PROVEAN

Benign

-2.1

REVEL

Uncertain

0.64

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.017

Polyphen

0.90

Vest4

0.19

MVP

0.70

MPC

0.75

ClinPred

0.13

GERP RS

3.9

Varity_R

0.41

gMVP

0.82

Mutation Taster

=87/13

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over