chr1-23795771-C-T

Variant names:

• chr1-23795771-C-T
• rs1803612
• NM_001008216.2:c.*178G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BS1_Supporting BS2

The NM_001008216.2(GALE):​c.*178G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000718 in 650,442 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00057 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00076 (2 hom.)
• Consequence: GALE NM_001008216.2 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.131
• Publications: 1 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000571 (87/152286) while in subpopulation NFE AF = 0.00097 (66/68026). AF 95% confidence interval is 0.000782. There are 0 homozygotes in GnomAd4. There are 38 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAdExome4 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALE	NM_001008216.2	MANE Select	c.*178G>A		3_prime_UTR	Exon 12 of 12	NP_001008217.1	A0A384NL38
	GALE	NM_000403.4		c.*178G>A		3_prime_UTR	Exon 12 of 12	NP_000394.2	Q14376-1
	GALE	NM_001127621.2		c.*178G>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.*178G>A		3_prime_UTR	Exon 12 of 12	ENSP00000483375.1	Q14376-1
	GALE	ENST00000374497.7	TSL:1	c.*178G>A		3_prime_UTR	Exon 12 of 12	ENSP00000363621.3	Q14376-1
	GALE	ENST00000854948.1		c.*178G>A		3_prime_UTR	Exon 11 of 11	ENSP00000525007.1

Frequencies

GnomAD3 genomes AF: 0.000572 AC: 87 AN: 152168 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000970

Gnomad OTH AF: 0.000957

GnomAD4 exome AF: 0.000763 AC: 380 AN: 498156 Hom.: 2 Cov.: 5 AF XY: 0.000735 AC XY: 195 AN XY: 265204

African (AFR) AF: 0.000294 AC: 4 AN: 13604

American (AMR) AF: 0.000439 AC: 11 AN: 25040

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15332

East Asian (EAS) AF: 0.00 AC: 0 AN: 31660

South Asian (SAS) AF: 0.000697 AC: 35 AN: 50186

European-Finnish (FIN) AF: 0.000488 AC: 20 AN: 40990

Middle Eastern (MID) AF: 0.00381 AC: 8 AN: 2102

European-Non Finnish (NFE) AF: 0.000950 AC: 277 AN: 291598

Other (OTH) AF: 0.000904 AC: 25 AN: 27644

GnomAD4 genome AF: 0.000571 AC: 87 AN: 152286 Hom.: 0 Cov.: 32 AF XY: 0.000510 AC XY: 38 AN XY: 74454

African (AFR) AF: 0.000144 AC: 6 AN: 41562

American (AMR) AF: 0.000654 AC: 10 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10606

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000970 AC: 66 AN: 68026

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.000847 Hom.: 0

Bravo AF: 0.000597

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	-0.83
CADD	Benign	3.2
DANN	Benign	0.71
PhyloP100		-0.13
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1803612; hg19: chr1-24122261;