rs743554

chr17-75758167-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000154.2(GALK1):c.1108-40C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,609,576 control chromosomes in the GnomAD database, including 19,145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2246 hom., cov: 33)
  • Exomes 𝑓: 0.15 (16899 hom.)
• Consequence: GALK1 NM_000154.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.441

Genes affected

GALK1 (HGNC:4118): (galactokinase 1) Galactokinase is a major enzyme for the metabolism of galactose and its deficiency causes congenital cataracts during infancy and presenile cataracts in the adult population. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 17-75758167-G-A is Benign according to our data. Variant chr17-75758167-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1180482.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALK1	NM_000154.2	c.1108-40C>T		intron_variant		ENST00000588479.6
GALK1	NM_001381985.1	c.1108-40C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALK1	ENST00000588479.6	c.1108-40C>T		intron_variant		1	NM_000154.2	P1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24961 AN: 152070 Hom.: 2241 Cov.: 33

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.0148

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.149

GnomAD3 exomes AF: 0.144 AC: 33923 AN: 236046 Hom.: 2712 AF XY: 0.148 AC XY: 19134 AN XY: 129556

Gnomad AFR exome AF: 0.223

Gnomad AMR exome AF: 0.0968

Gnomad ASJ exome AF: 0.171

Gnomad EAS exome AF: 0.0114

Gnomad SAS exome AF: 0.174

Gnomad FIN exome AF: 0.152

Gnomad NFE exome AF: 0.157

Gnomad OTH exome AF: 0.149

GnomAD4 exome AF: 0.148 AC: 215599 AN: 1457388 Hom.: 16899 Cov.: 35 AF XY: 0.149 AC XY: 108023 AN XY: 724906

Gnomad4 AFR exome AF: 0.231

Gnomad4 AMR exome AF: 0.100

Gnomad4 ASJ exome AF: 0.168

Gnomad4 EAS exome AF: 0.0101

Gnomad4 SAS exome AF: 0.174

Gnomad4 FIN exome AF: 0.147

Gnomad4 NFE exome AF: 0.150

Gnomad4 OTH exome AF: 0.147

GnomAD4 genome AF: 0.164 AC: 24982 AN: 152188 Hom.: 2246 Cov.: 33 AF XY: 0.160 AC XY: 11906 AN XY: 74396

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.0149

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.152

Gnomad4 OTH AF: 0.150

Alfa AF: 0.155 Hom.: 633

Bravo AF: 0.165

Asia WGS AF: 0.104 AC: 362 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

- -

Deficiency of galactokinase Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 08, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	6.1
Dann	Benign	0.89

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

Publications

LitVar

Other links and lift over

dbSNP: rs743554; hg19: chr17-73754248;