rs760941

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000617979.5(GALE):c.873+13G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000945 in 1,392,538 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0013 ( 2 hom., cov: 14)

Exomes 𝑓: 0.00092 ( 1 hom. )

Consequence

GALE
ENST00000617979.5 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

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-G is Benign according to our data. Variant chr1-23796496-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 402890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00127 (138/108690) while in subpopulation NFE AF= 0.00185 (97/52450). AF 95% confidence interval is 0.00155. There are 2 homozygotes in gnomad4. There are 69 alleles in male gnomad4 subpopulation. Median coverage is 14. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
GALE	NM_001008216.2 linkuse as main transcript	c.873+13G>C	intron_variant	ENST00000617979.5	NP_001008217.1
GALE	NM_000403.4 linkuse as main transcript	c.873+13G>C	intron_variant		NP_000394.2
GALE	NM_001127621.2 linkuse as main transcript	c.873+13G>C	intron_variant		NP_001121093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GALE	ENST00000617979.5 linkuse as main transcript	c.873+13G>C		intron_variant		1	NM_001008216.2	ENSP00000483375	P1	Q14376-1

Frequencies

GnomAD3 genomes

AF:

0.00126

AC:

137

AN:

108624

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000664

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000634

Gnomad ASJ

AF:

0.00145

Gnomad EAS

AF:

0.000805

Gnomad SAS

AF:

0.00115

Gnomad FIN

AF:

0.000417

Gnomad MID

AF:

0.00410

Gnomad NFE

AF:

0.00185

Gnomad OTH

AF:

0.000694

GnomAD3 exomes

AF:

0.00156

AC:

350

AN:

224046

Hom.:

AF XY:

0.00139

AC XY:

170

AN XY:

122282

show subpopulations

Gnomad AFR exome

AF:

0.000926

Gnomad AMR exome

AF:

0.000851

Gnomad ASJ exome

AF:

0.000637

Gnomad EAS exome

AF:

0.00145

Gnomad SAS exome

AF:

0.000986

Gnomad FIN exome

AF:

0.00292

Gnomad NFE exome

AF:

0.00193

Gnomad OTH exome

AF:

0.000906

GnomAD4 exome

AF:

0.000918

AC:

1178

AN:

1283848

Hom.:

Cov.:

AF XY:

0.000887

AC XY:

568

AN XY:

640066

show subpopulations

Gnomad4 AFR exome

AF:

0.000184

Gnomad4 AMR exome

AF:

0.000896

Gnomad4 ASJ exome

AF:

0.000132

Gnomad4 EAS exome

AF:

0.000641

Gnomad4 SAS exome

AF:

0.000531

Gnomad4 FIN exome

AF:

0.00158

Gnomad4 NFE exome

AF:

0.000962

Gnomad4 OTH exome

AF:

0.000961

GnomAD4 genome

AF:

0.00127

AC:

138

AN:

108690

Hom.:

Cov.:

AF XY:

0.00131

AC XY:

AN XY:

52594

show subpopulations

Gnomad4 AFR

AF:

0.000701

Gnomad4 AMR

AF:

0.000633

Gnomad4 ASJ

AF:

0.00145

Gnomad4 EAS

AF:

0.000807

Gnomad4 SAS

AF:

0.00115

Gnomad4 FIN

AF:

0.000417

Gnomad4 NFE

AF:

0.00185

Gnomad4 OTH

AF:

0.000689

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

UDPglucose-4-epimerase deficiency

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 19, 2024	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Same variant as above. Gene associated with epimerase deficiency galactosemia - Infants with the profound generalized form who are on a diet containing galactose/lactose manifest hypotonia, poor feeding, vomiting, weight loss, jaundice, hepatomegaly, liver dysfunction, aminoaciduria, and cataracts. Frequency and location of variant suggest benign -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.78

DANN

Benign

0.68

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