rs62557482

Variant names:

• chr9-34646526-C-T
• rs62557482
• ENST00000605275.1:n.209-151C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000605275.1(GALT):​n.209-151C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00147 in 742,896 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (1 hom.)
• Consequence: GALT ENST00000605275.1 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.174

Genes affected

GALT (HGNC:4135): (galactose-1-phosphate uridylyltransferase) Galactose-1-phosphate uridyl transferase (GALT) catalyzes the second step of the Leloir pathway of galactose metabolism, namely the conversion of UDP-glucose + galactose-1-phosphate to glucose-1-phosphate + UDP-galactose. The absence of this enzyme results in classic galactosemia in humans and can be fatal in the newborn period if lactose is not removed from the diet. The pathophysiology of galactosemia has not been clearly defined. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALT	ENST00000605275.1	n.209-151C>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.00123 AC: 187 AN: 152236 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000753

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00218

Gnomad OTH AF: 0.00143

GnomAD4 exome AF: 0.00153 AC: 905 AN: 590542 Hom.: 1 AF XY: 0.00153 AC XY: 479 AN XY: 312904

Gnomad4 AFR exome AF: 0.000187

Gnomad4 AMR exome AF: 0.000928

Gnomad4 ASJ exome AF: 0.000282

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000753

Gnomad4 FIN exome AF: 0.000988

Gnomad4 NFE exome AF: 0.00211

Gnomad4 OTH exome AF: 0.000939

GnomAD4 genome AF: 0.00123 AC: 187 AN: 152354 Hom.: 0 Cov.: 32 AF XY: 0.00109 AC XY: 81 AN XY: 74498

Gnomad4 AFR AF: 0.000216

Gnomad4 AMR AF: 0.000653

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.000753

Gnomad4 NFE AF: 0.00218

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00185 Hom.: 0

Bravo AF: 0.00129

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 21, 2022

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: GALT c.-179C>T is located in the untranscribed region upstream of the GALT gene region. The variant allele was found at a frequency of 0.0012 in 31388 control chromosomes, predominantly at a frequency of 0.002 within the Non-Finnish European subpopulation in the gnomAD database (Genomes data). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.-179C>T in individuals affected with Galactosemia and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.98
DANN	Benign	0.51

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs62557482; hg19: chr9-34646523;