1-23796496-C-T

Position:

chr1-23796496-C-T

Variant summary

Our verdict is Benign. Variant got -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:6

Conservation

PhyloP100: -0.798

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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	MANE
GALE	NM_001008216.2 linkuse as main transcript	c.873+13G>A	intron_variant	ENST00000617979.5
GALE	NM_000403.4 linkuse as main transcript	c.873+13G>A	intron_variant
GALE	NM_001127621.2 linkuse as main transcript	c.873+13G>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALE	ENST00000617979.5 linkuse as main transcript	c.873+13G>A		intron_variant		1	NM_001008216.2	P1	Q14376-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

72545

AN:

108194

Hom.:

19762

Cov.:

FAILED QC

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

GnomAD3 exomes

AF:

0.643

AC:

144003

AN:

224046

Hom.:

42759

AF XY:

0.648

AC XY:

79202

AN XY:

122282

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 SAS exome

AF:

0.736

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

Gnomad4 AFR exome

AF:

0.569

Gnomad4 AMR exome

AF:

0.696

Gnomad4 ASJ exome

AF:

0.643

Gnomad4 EAS exome

AF:

0.683

Gnomad4 SAS exome

AF:

0.759

Gnomad4 FIN exome

AF:

0.656

Gnomad4 NFE exome

AF:

0.649

Gnomad4 OTH exome

AF:

0.657

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

Gnomad4 AFR

AF:

0.621

Gnomad4 AMR

AF:

0.694

Gnomad4 ASJ

AF:

0.676

Gnomad4 EAS

AF:

0.652

Gnomad4 SAS

AF:

0.765

Gnomad4 FIN

AF:

0.681

Gnomad4 NFE

AF:

0.682

Gnomad4 OTH

AF:

0.676

Alfa

AF:

0.474

Hom.:

2487

Bravo

AF:

0.544

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

UDPglucose-4-epimerase deficiency

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 23, 2018	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.8

DANN

Benign

0.72

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