rs743554

Variant names:

• chr17-75758167-G-A
• rs743554
• NM_000154.2:c.1108-40C>T

Variant summary

Our verdict is Benign. The variant received -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:3
• Conservation: PhyloP100: 0.441
• Publications: 29 publications found

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]

GALK1 Gene-Disease associations (from GenCC):

• galactokinase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Myriad Women’s Health, Labcorp Genetics (formerly Invitae), G2P, Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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 rank	MANE	Protein	UniProt
GALK1	NM_000154.2	c.1108-40C>T		intron_variant	Intron 7 of 7	ENST00000588479.6	NP_000145.1
GALK1	NM_001381985.1	c.1108-40C>T		intron_variant	Intron 7 of 8		NP_001368914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALK1	ENST00000588479.6	c.1108-40C>T		intron_variant	Intron 7 of 7	1	NM_000154.2	ENSP00000465930.1

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

GnomAD2 exomes AF: 0.144 AC: 33923 AN: 236046 AF XY: 0.148

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 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

African (AFR) AF: 0.231 AC: 7736 AN: 33458

American (AMR) AF: 0.100 AC: 4444 AN: 44396

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 4378 AN: 26062

East Asian (EAS) AF: 0.0101 AC: 401 AN: 39630

South Asian (SAS) AF: 0.174 AC: 15007 AN: 86054

European-Finnish (FIN) AF: 0.147 AC: 7503 AN: 51030

Middle Eastern (MID) AF: 0.180 AC: 1036 AN: 5744

European-Non Finnish (NFE) AF: 0.150 AC: 166262 AN: 1110902

Other (OTH) AF: 0.147 AC: 8832 AN: 60112

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

African (AFR) AF: 0.223 AC: 9246 AN: 41514

American (AMR) AF: 0.121 AC: 1859 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 540 AN: 3470

East Asian (EAS) AF: 0.0149 AC: 77 AN: 5174

South Asian (SAS) AF: 0.155 AC: 750 AN: 4832

European-Finnish (FIN) AF: 0.149 AC: 1581 AN: 10612

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10306 AN: 67962

Other (OTH) AF: 0.150 AC: 316 AN: 2112

Alfa AF: 0.156 Hom.: 772

Bravo AF: 0.165

Asia WGS AF: 0.104 AC: 362 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 29, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Deficiency of galactokinase Benign:1

Jul 08, 2021

Genome-Nilou Lab

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.1
DANN	Benign	0.89
PhyloP100		0.44
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs743554; hg19: chr17-73754248;