rs76160162

chr17-75758360-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_000154.2(GALK1):c.957G>A(p.Glu319=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000737 in 1,592,564 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0037 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00042 (6 hom.)
• Consequence: GALK1 NM_000154.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.06

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 17-75758360-C-T is Benign according to our data. Variant chr17-75758360-C-T is described in ClinVar as [Benign]. Clinvar id is 459630.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.06 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00372 (567/152364) while in subpopulation AFR AF= 0.0129 (536/41592). AF 95% confidence interval is 0.012. There are 2 homozygotes in gnomad4. There are 277 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALK1	NM_000154.2	c.957G>A	p.Glu319=	synonymous_variant	7/8	ENST00000588479.6
GALK1	NM_001381985.1	c.957G>A	p.Glu319=	synonymous_variant	7/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALK1	ENST00000588479.6	c.957G>A	p.Glu319=	synonymous_variant	7/8	1	NM_000154.2	P1

Frequencies

GnomAD3 genomes AF: 0.00376 AC: 572 AN: 152246 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.0130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.000895 AC: 189 AN: 211200 Hom.: 1 AF XY: 0.000620 AC XY: 71 AN XY: 114516

Gnomad AFR exome AF: 0.0132

Gnomad AMR exome AF: 0.000596

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000371

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000108

Gnomad OTH exome AF: 0.000564

GnomAD4 exome AF: 0.000421 AC: 606 AN: 1440200 Hom.: 6 Cov.: 34 AF XY: 0.000330 AC XY: 236 AN XY: 714510

Gnomad4 AFR exome AF: 0.0153

Gnomad4 AMR exome AF: 0.000778

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000120

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000272

Gnomad4 OTH exome AF: 0.000990

GnomAD4 genome AF: 0.00372 AC: 567 AN: 152364 Hom.: 2 Cov.: 33 AF XY: 0.00372 AC XY: 277 AN XY: 74508

Gnomad4 AFR AF: 0.0129

Gnomad4 AMR AF: 0.00163

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00177 Hom.: 0

Bravo AF: 0.00445

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Deficiency of galactokinase Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
Cadd	Benign	11
Dann	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs76160162; hg19: chr17-73754441; COSMIC: COSV99564003; COSMIC: COSV99564003;