1-23796496-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001008216.2(GALE):c.873+13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 1,284,454 control chromosomes in the GnomAD database, including 246,405 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.67 ( 19768 hom., cov: 14)

Exomes 𝑓: 0.66 ( 246405 hom. )

Failed GnomAD Quality Control

Consequence

GALE
NM_001008216.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.798

Publications

9 publications found

Variant links:

Genes affected

GALE (HGNC:4116): (UDP-galactose-4-epimerase) This gene encodes UDP-galactose-4-epimerase which catalyzes two distinct but analogous reactions: the epimerization of UDP-glucose to UDP-galactose, and the epimerization of UDP-N-acetylglucosamine to UDP-N-acetylgalactosamine. The bifunctional nature of the enzyme has the important metabolic consequence that mutant cells (or individuals) are dependent not only on exogenous galactose, but also on exogenous N-acetylgalactosamine as a necessary precursor for the synthesis of glycoproteins and glycolipids. Mutations in this gene result in epimerase-deficiency galactosemia, also referred to as galactosemia type 3, a disease characterized by liver damage, early-onset cataracts, deafness and cognitive disability, with symptoms ranging from mild ('peripheral' form) to severe ('generalized' form). Multiple alternatively spliced transcripts encoding the same protein have been identified. [provided by RefSeq, Jul 2008]

GALE Gene-Disease associations (from GenCC):

galactose epimerase deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Ambry Genetics

GALE links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 1-23796496-C-T is Benign according to our data. Variant chr1-23796496-C-T is described in ClinVar as Benign. ClinVar VariationId is 92889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
GALE	NM_001008216.2 link	c.873+13G>A	intron_variant	Intron 10 of 11	ENST00000617979.5	NP_001008217.1
GALE	NM_000403.4 link	c.873+13G>A	intron_variant	Intron 10 of 11		NP_000394.2
GALE	NM_001127621.2 link	c.873+13G>A	intron_variant	Intron 9 of 10		NP_001121093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALE	ENST00000617979.5 link	c.873+13G>A		intron_variant	Intron 10 of 11	1	NM_001008216.2	ENSP00000483375.1

Frequencies

GnomAD3 genomes

AF:

0.671

AC:

72545

AN:

108194

Hom.:

19762

Cov.:

show subpopulations

Gnomad AFR

AF:

0.621

Gnomad AMI

AF:

0.680

Gnomad AMR

AF:

0.693

Gnomad ASJ

AF:

0.676

Gnomad EAS

AF:

0.653

Gnomad SAS

AF:

0.765

Gnomad FIN

AF:

0.681

Gnomad MID

AF:

0.754

Gnomad NFE

AF:

0.682

Gnomad OTH

AF:

0.677

GnomAD2 exomes

AF:

0.643

AC:

144003

AN:

224046

AF XY:

0.648

show subpopulations

Gnomad AFR exome

AF:

0.544

Gnomad AMR exome

AF:

0.702

Gnomad ASJ exome

AF:

0.594

Gnomad EAS exome

AF:

0.632

Gnomad FIN exome

AF:

0.625

Gnomad NFE exome

AF:

0.619

Gnomad OTH exome

AF:

0.632

GnomAD4 exome

AF:

0.657

AC:

844399

AN:

1284454

Hom.:

246405

Cov.:

AF XY:

0.661

AC XY:

423320

AN XY:

640424

show subpopulations

African (AFR)

AF:

0.569

AC:

15488

AN:

27198

American (AMR)

AF:

0.696

AC:

28792

AN:

41392

Ashkenazi Jewish (ASJ)

AF:

0.643

AC:

14618

AN:

22724

East Asian (EAS)

AF:

0.683

AC:

23505

AN:

34406

South Asian (SAS)

AF:

0.759

AC:

61631

AN:

81248

European-Finnish (FIN)

AF:

0.656

AC:

29110

AN:

44388

Middle Eastern (MID)

AF:

0.713

AC:

2728

AN:

3826

European-Non Finnish (NFE)

AF:

0.649

AC:

634329

AN:

977222

Other (OTH)

AF:

0.657

AC:

34198

AN:

52050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

18123

36246

54370

72493

90616

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17682

35364

53046

70728

88410

<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

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.670

AC:

72579

AN:

108260

Hom.:

19768

Cov.:

AF XY:

0.673

AC XY:

35219

AN XY:

52368

show subpopulations

African (AFR)

AF:

0.621

AC:

15856

AN:

25548

American (AMR)

AF:

0.694

AC:

7650

AN:

11026

Ashkenazi Jewish (ASJ)

AF:

0.676

AC:

1866

AN:

2760

East Asian (EAS)

AF:

0.652

AC:

2409

AN:

3694

South Asian (SAS)

AF:

0.765

AC:

2652

AN:

3466

European-Finnish (FIN)

AF:

0.681

AC:

4873

AN:

7154

Middle Eastern (MID)

AF:

0.752

AC:

167

AN:

222

European-Non Finnish (NFE)

AF:

0.682

AC:

35685

AN:

52292

Other (OTH)

AF:

0.676

AC:

976

AN:

1444

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

1504

3008

4511

6015

7519

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

628

1256

1884

2512

3140

<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:

0.474

Hom.:

4109

Bravo

AF:

0.544

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

UDPglucose-4-epimerase deficiency

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified

Benign:2

Mar 23, 2018

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

May 11, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.8

(source)

DANN

Benign

0.72

PhyloP100

-0.80

PromoterAI

0.016

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over