rs3180383

Variant names:

• chr1-23796202-G-A
• rs3180383
• NM_001008216.2:c.937C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-23796202-G-A
• chr1-23796202-G-C
• chr1-23796202-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001008216.2(GALE):​c.937C>T​(p.Leu313Leu) variant causes a synonymous change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GALE NM_001008216.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.28
• Publications: 8 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: Ambry Genetics, ClinGen, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 1-23796202-G-A is Benign according to our data. Variant chr1-23796202-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3338950.Status of the report is criteria_provided_single_submitter, 1 stars.

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.937C>T	p.Leu313Leu	synonymous	Exon 11 of 12	NP_001008217.1	A0A384NL38
	GALE	NM_000403.4		c.937C>T	p.Leu313Leu	synonymous	Exon 11 of 12	NP_000394.2	Q14376-1
	GALE	NM_001127621.2		c.937C>T	p.Leu313Leu	synonymous	Exon 10 of 11	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.937C>T	p.Leu313Leu	synonymous	Exon 11 of 12	ENSP00000483375.1	Q14376-1
	GALE	ENST00000374497.7	TSL:1	c.937C>T	p.Leu313Leu	synonymous	Exon 11 of 12	ENSP00000363621.3	Q14376-1
	GALE	ENST00000854948.1		c.937C>T	p.Leu313Leu	synonymous	Exon 10 of 11	ENSP00000525007.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	6.3
DANN	Benign	0.82
PhyloP100		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=44/56	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3180383; hg19: chr1-24122692;