dbSNP rs760941: GALE:c.873+13G>C (chr1-23796496-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001008216.2(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
NM_001008216.2 intron

Scores

Clinical Significance

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

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: G2P, ClinGen, Labcorp Genetics (formerly Invitae), 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-G is Benign according to our data. Variant chr1-23796496-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId 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 the male GnomAd4 subpopulation. Median coverage is 14. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001008216.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GALE	NM_001008216.2	MANE Select	c.873+13G>C	intron	N/A	NP_001008217.1	A0A384NL38
GALE	NM_000403.4		c.873+13G>C	intron	N/A	NP_000394.2	Q14376-1
GALE	NM_001127621.2		c.873+13G>C	intron	N/A	NP_001121093.1	A0A384NL38

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GALE	ENST00000617979.5	TSL:1 MANE Select	c.873+13G>C	intron	N/A	ENSP00000483375.1	Q14376-1
GALE	ENST00000374497.7	TSL:1	c.873+13G>C	intron	N/A	ENSP00000363621.3	Q14376-1
GALE	ENST00000854948.1		c.873+13G>C	intron	N/A	ENSP00000525007.1

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

GnomAD2 exomes

AF:

0.00156

AC:

350

AN:

224046

AF XY:

0.00139

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 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

African (AFR)

AF:

0.000184

AC:

AN:

27186

American (AMR)

AF:

0.000896

AC:

AN:

41308

Ashkenazi Jewish (ASJ)

AF:

0.000132

AC:

AN:

22706

East Asian (EAS)

AF:

0.000641

AC:

AN:

34336

South Asian (SAS)

AF:

0.000531

AC:

AN:

81028

European-Finnish (FIN)

AF:

0.00158

AC:

AN:

44332

Middle Eastern (MID)

AF:

0.00210

AC:

AN:

3818

European-Non Finnish (NFE)

AF:

0.000962

AC:

940

AN:

977122

Other (OTH)

AF:

0.000961

AC:

AN:

52012

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

105

157

210

262

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<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

AF:

0.00127

AC:

138

AN:

108690

Hom.:

Cov.:

AF XY:

0.00131

AC XY:

AN XY:

52594

show subpopulations

African (AFR)

AF:

0.000701

AC:

AN:

25692

American (AMR)

AF:

0.000633

AC:

AN:

11060

Ashkenazi Jewish (ASJ)

AF:

0.00145

AC:

AN:

2768

East Asian (EAS)

AF:

0.000807

AC:

AN:

3718

South Asian (SAS)

AF:

0.00115

AC:

AN:

3480

European-Finnish (FIN)

AF:

0.000417

AC:

AN:

7188

Middle Eastern (MID)

AF:

0.00442

AC:

AN:

226

European-Non Finnish (NFE)

AF:

0.00185

AC:

AN:

52450

Other (OTH)

AF:

0.000689

AC:

AN:

1452

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.402

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

4109

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

UDPglucose-4-epimerase deficiency (2)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.78

(source)

DANN

Benign

0.68

PhyloP100

-0.80

PromoterAI

-0.0081

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over