rs7211385

Positions:

• chr17-75764063-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000154.2(GALK1):​c.189G>A​(p.Leu63=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00685 in 1,588,968 control chromosomes in the GnomAD database, including 613 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.036 (339 hom., cov: 33)
  • Exomes 𝑓: 0.0038 (274 hom.)
• Consequence: GALK1 NM_000154.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.640

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=-0.53).
• BP6: Variant 17-75764063-C-T is Benign according to our data. Variant chr17-75764063-C-T is described in ClinVar as [Benign]. Clinvar id is 92514.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.64 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GALK1	NM_000154.2	c.189G>A	p.Leu63=	synonymous_variant	2/8	ENST00000588479.6	NP_000145.1
GALK1	NM_001381985.1	c.189G>A	p.Leu63=	synonymous_variant	2/9		NP_001368914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GALK1	ENST00000588479.6	c.189G>A	p.Leu63=	synonymous_variant	2/8	1	NM_000154.2	ENSP00000465930	P1

Frequencies

GnomAD3 genomes AF: 0.0359 AC: 5461 AN: 152128 Hom.: 337 Cov.: 33

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0121

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000529

Gnomad OTH AF: 0.0278

GnomAD3 exomes AF: 0.00898 AC: 1857 AN: 206882 Hom.: 91 AF XY: 0.00673 AC XY: 758 AN XY: 112652

Gnomad AFR exome AF: 0.125

Gnomad AMR exome AF: 0.00579

Gnomad ASJ exome AF: 0.000768

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000291

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000557

Gnomad OTH exome AF: 0.00245

GnomAD4 exome AF: 0.00376 AC: 5399 AN: 1436722 Hom.: 274 Cov.: 32 AF XY: 0.00323 AC XY: 2301 AN XY: 713380

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.00654

Gnomad4 ASJ exome AF: 0.00117

Gnomad4 EAS exome AF: 0.0000258

Gnomad4 SAS exome AF: 0.000227

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000322

Gnomad4 OTH exome AF: 0.00830

GnomAD4 genome AF: 0.0360 AC: 5483 AN: 152246 Hom.: 339 Cov.: 33 AF XY: 0.0347 AC XY: 2582 AN XY: 74436

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.0121

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00103

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000530

Gnomad4 OTH AF: 0.0275

Alfa AF: 0.0103 Hom.: 102

Bravo AF: 0.0403

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Deficiency of galactokinase Benign:3

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jan 16, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	6.9
DANN	Benign	0.70

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: rs7211385; hg19: chr17-73760144;