chr1-23795791-C-T

Variant names:

• chr1-23795791-C-T
• rs1343467826
• NM_001008216.2:c.*158G>A

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.*158G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GALE NM_001008216.2 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0250
• 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]

LYPLA2 (HGNC:6738): (lysophospholipase 2) Lysophospholipases are enzymes that act on biological membranes to regulate the multifunctional lysophospholipids. There are alternatively spliced transcript variants described for this gene but the full length nature is not known yet. [provided by RefSeq, Jul 2008]

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=-0.6).

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.*158G>A		3_prime_UTR	Exon 12 of 12	NP_001008217.1	A0A384NL38
	GALE	NM_000403.4		c.*158G>A		3_prime_UTR	Exon 12 of 12	NP_000394.2	Q14376-1
	GALE	NM_001127621.2		c.*158G>A		3_prime_UTR	Exon 11 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.*158G>A		3_prime_UTR	Exon 12 of 12	ENSP00000483375.1	Q14376-1
	GALE	ENST00000374497.7	TSL:1	c.*158G>A		3_prime_UTR	Exon 12 of 12	ENSP00000363621.3	Q14376-1
	GALE	ENST00000854948.1		c.*158G>A		3_prime_UTR	Exon 11 of 11	ENSP00000525007.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 554916 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 296796

African (AFR) AF: 0.00 AC: 0 AN: 15270

American (AMR) AF: 0.00 AC: 0 AN: 31458

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17422

East Asian (EAS) AF: 0.00 AC: 0 AN: 32046

South Asian (SAS) AF: 0.00 AC: 0 AN: 56748

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2326

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 324516

Other (OTH) AF: 0.00 AC: 0 AN: 29858

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	-0.60
CADD	Benign	8.1
DANN	Benign	0.83
PhyloP100		-0.025
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs1343467826; hg19: chr1-24122281;