rs1553130228

Variant names:

• chr1-23796503-G-A
• rs1553130228
• NM_001008216.2:c.873+6C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-23796503-G-A
• chr1-23796503-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001008216.2(GALE):​c.873+6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000986 in 1,013,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 9.9e-7 (0 hom.)
• Consequence: GALE NM_001008216.2 splice_region, intron
• Scores: Splicing: ADA: 0.0004778
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.626
• Publications: 0 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALE	NM_001008216.2	MANE Select	c.873+6C>T		splice_region intron	N/A	NP_001008217.1	A0A384NL38
	GALE	NM_000403.4		c.873+6C>T		splice_region intron	N/A	NP_000394.2	Q14376-1
	GALE	NM_001127621.2		c.873+6C>T		splice_region intron	N/A	NP_001121093.1	A0A384NL38

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALE	ENST00000617979.5	TSL:1 MANE Select	c.873+6C>T		splice_region intron	N/A	ENSP00000483375.1	Q14376-1
	GALE	ENST00000374497.7	TSL:1	c.873+6C>T		splice_region intron	N/A	ENSP00000363621.3	Q14376-1
	GALE	ENST00000854948.1		c.873+6C>T		splice_region intron	N/A	ENSP00000525007.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 9.86e-7 AC: 1 AN: 1013886 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 513246

African (AFR) AF: 0.00 AC: 0 AN: 23478

American (AMR) AF: 0.00 AC: 0 AN: 38916

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17814

East Asian (EAS) AF: 0.0000429 AC: 1 AN: 23294

South Asian (SAS) AF: 0.00 AC: 0 AN: 78450

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37758

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2840

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 751552

Other (OTH) AF: 0.00 AC: 0 AN: 39784

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	UDPglucose-4-epimerase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	8.5
DANN	Benign	0.75
PhyloP100		0.63
PromoterAI		-0.051	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00048
dbscSNV1_RF	Benign	0.020
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

Other links and lift over

dbSNP: rs1553130228; hg19: chr1-24122993;