rs143694860

Positions:

chr1-23796227-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001008216.2(GALE):c.912G>A(p.Val304=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000754 in 1,614,144 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0023 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00059 ( 3 hom. )

Consequence

GALE
NM_001008216.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.0890

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 1-23796227-C-T is Benign according to our data. Variant chr1-23796227-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 92891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.089 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00234 (357/152284) while in subpopulation AFR AF= 0.00652 (271/41560). AF 95% confidence interval is 0.00588. There are 4 homozygotes in gnomad4. There are 163 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GALE	NM_001008216.2 linkuse as main transcript	c.912G>A	p.Val304=	synonymous_variant	11/12	ENST00000617979.5	NP_001008217.1
GALE	NM_000403.4 linkuse as main transcript	c.912G>A	p.Val304=	synonymous_variant	11/12		NP_000394.2
GALE	NM_001127621.2 linkuse as main transcript	c.912G>A	p.Val304=	synonymous_variant	10/11		NP_001121093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GALE	ENST00000617979.5 linkuse as main transcript	c.912G>A	p.Val304=	synonymous_variant	11/12	1	NM_001008216.2	ENSP00000483375	P1	Q14376-1

Frequencies

GnomAD3 genomes

AF:

0.00235

AC:

357

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00654

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.00288

GnomAD3 exomes

AF:

0.00105

AC:

265

AN:

251298

Hom.:

AF XY:

0.000957

AC XY:

130

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.00634

Gnomad AMR exome

AF:

0.00136

Gnomad ASJ exome

AF:

0.00427

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000475

Gnomad OTH exome

AF:

0.00277

GnomAD4 exome

AF:

0.000588

AC:

860

AN:

1461860

Hom.:

Cov.:

AF XY:

0.000557

AC XY:

405

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00484

Gnomad4 AMR exome

AF:

0.00148

Gnomad4 ASJ exome

AF:

0.00471

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000362

Gnomad4 OTH exome

AF:

0.00146

GnomAD4 genome

AF:

0.00234

AC:

357

AN:

152284

Hom.:

Cov.:

AF XY:

0.00219

AC XY:

163

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00652

Gnomad4 AMR

AF:

0.00248

Gnomad4 ASJ

AF:

0.00576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.00285

Alfa

AF:

0.00162

Hom.:

Bravo

AF:

0.00250

EpiCase

AF:

0.000709

EpiControl

AF:

0.000533

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 27, 2018	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	GALE: BP4, BP7, BS2 -

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 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.84

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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