Variant 15-42287713-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.224A>G(p.Tyr75Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000434 in 1,611,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

GANC
NM_198141.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.194

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=0.17313951).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GANC	NM_198141.3 linkuse as main transcript	c.224A>G	p.Tyr75Cys	missense_variant	4/24	ENST00000318010.13	NP_937784.2
GANC	NM_001393928.1 linkuse as main transcript	c.224A>G	p.Tyr75Cys	missense_variant	5/25		NP_001380857.1
GANC	NM_001393929.1 linkuse as main transcript	c.224A>G	p.Tyr75Cys	missense_variant	5/25		NP_001380858.1
GANC	NM_001301409.2 linkuse as main transcript	c.224A>G	p.Tyr75Cys	missense_variant	5/12		NP_001288338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GANC	ENST00000318010.13 linkuse as main transcript	c.224A>G	p.Tyr75Cys	missense_variant	4/24	1	NM_198141.3	ENSP00000326227	P1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000201

AC:

AN:

249070

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

134718

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000442

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000473

AC:

AN:

1459354

Hom.:

Cov.:

AF XY:

0.0000510

AC XY:

AN XY:

725994

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000612

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

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

Nov 08, 2022

The c.224A>G (p.Y75C) alteration is located in exon 4 (coding exon 4) of the GANC gene. This alteration results from a A to G substitution at nucleotide position 224, causing the tyrosine (Y) at amino acid position 75 to be replaced by a cysteine (C). 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

0.062

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.30

T;.;T

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.75

T;T;T

M_CAP

Benign

0.0052

MetaRNN

Benign

0.17

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

.;.;L

MutationTaster

Benign

0.92

D;D

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-4.7

D;D;D

REVEL

Benign

0.13

Sift

Benign

0.066

T;T;T

Sift4G

Benign

0.083

T;T;T

Polyphen

0.0050

.;.;B

Vest4

0.20, 0.21

MutPred

0.46

Loss of sheet (P = 0.0043);Loss of sheet (P = 0.0043);Loss of sheet (P = 0.0043);

MVP

0.16

MPC

0.022

ClinPred

0.18

GERP RS

0.033

Varity_R

0.074

gMVP

0.51

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