rs1343467826

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-23795791-C-A
• chr1-23795791-C-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.*158G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000018 in 554,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: GALE NM_001008216.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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=-0.57).

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000180 AC: 1 AN: 554914 Hom.: 0 Cov.: 6 AF XY: 0.00000337 AC XY: 1 AN XY: 296794

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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: 56746

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: 0.00000308 AC: 1 AN: 324516

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

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	7.6
DANN	Benign	0.85
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;