Variant 15-42308288-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198141.3(GANC):c.692A>G(p.His231Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000756 in 1,609,240 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 (★).

Frequency

Genomes: 𝑓 0.00044 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00079 ( 0 hom. )

Consequence

GANC
NM_198141.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.59

Variant links:

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]

GANC links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.19018453).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GANC	NM_198141.3 linkuse as main transcript	c.692A>G	p.His231Arg	missense_variant	8/24	ENST00000318010.13	NP_937784.2
GANC	NM_001393928.1 linkuse as main transcript	c.692A>G	p.His231Arg	missense_variant	9/25		NP_001380857.1
GANC	NM_001393929.1 linkuse as main transcript	c.692A>G	p.His231Arg	missense_variant	9/25		NP_001380858.1
GANC	NM_001301409.2 linkuse as main transcript	c.692A>G	p.His231Arg	missense_variant	9/12		NP_001288338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
GANC	ENST00000318010.13 linkuse as main transcript	c.692A>G	p.His231Arg	missense_variant	8/24	1	NM_198141.3	ENSP00000326227	P1
GANC	ENST00000566442.5 linkuse as main transcript	c.692A>G	p.His231Arg	missense_variant	9/12	2		ENSP00000454747
GANC	ENST00000567421.1 linkuse as main transcript	n.665A>G		non_coding_transcript_exon_variant	7/12	5

Frequencies

GnomAD3 genomes

AF:

0.000440

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000808

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000359

AC:

AN:

251038

Hom.:

AF XY:

0.000420

AC XY:

AN XY:

135662

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000647

Gnomad NFE exome

AF:

0.000617

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000789

AC:

1150

AN:

1457014

Hom.:

Cov.:

AF XY:

0.000760

AC XY:

551

AN XY:

724718

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000582

Gnomad4 NFE exome

AF:

0.000937

Gnomad4 OTH exome

AF:

0.00125

GnomAD4 genome

AF:

0.000440

AC:

AN:

152226

Hom.:

Cov.:

AF XY:

0.000350

AC XY:

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.000808

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000645

Hom.:

Bravo

AF:

0.000461

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000255

AC:

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

Jun 18, 2021

The c.692A>G (p.H231R) alteration is located in exon 8 (coding exon 8) of the GANC gene. This alteration results from a A to G substitution at nucleotide position 692, causing the histidine (H) at amino acid position 231 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.66

.;D

Eigen

Uncertain

0.19

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.84

T;D

M_CAP

Benign

0.063

MetaRNN

Benign

0.19

T;T

MetaSVM

Uncertain

0.066

MutationAssessor

Uncertain

2.1

.;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.74

PROVEAN

Pathogenic

-6.7

D;D

REVEL

Uncertain

0.43

Sift

Uncertain

0.028

D;D

Sift4G

Benign

0.34

T;T

Polyphen

0.23

.;B

Vest4

0.50

MVP

0.69

MPC

0.040

ClinPred

0.18

GERP RS

4.5

Varity_R

0.71

gMVP

0.90

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over