rs7211385

Variant names:

• chr17-75764063-C-T
• rs7211385
• NM_000154.2:c.189G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-75764063-C-T
• chr17-75764063-C-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000154.2(GALK1):​c.189G>A​(p.Leu63Leu) 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 (★★). Synonymous variant affecting the same amino acid position (i.e. L63L) has been classified as Likely 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
• Publications: 4 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: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Myriad Women’s Health, Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000154.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALK1	NM_000154.2	MANE Select	c.189G>A	p.Leu63Leu	synonymous	Exon 2 of 8	NP_000145.1	P51570
	GALK1	NM_001381985.1		c.189G>A	p.Leu63Leu	synonymous	Exon 2 of 9	NP_001368914.1	P51570

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALK1	ENST00000588479.6	TSL:1 MANE Select	c.189G>A	p.Leu63Leu	synonymous	Exon 2 of 8	ENSP00000465930.1	P51570
	GALK1	ENST00000586244.1	TSL:1	n.189G>A		non_coding_transcript_exon	Exon 2 of 4	ENSP00000468288.1	K7ERJ9
	GALK1	ENST00000864472.1		c.189G>A	p.Leu63Leu	synonymous	Exon 2 of 9	ENSP00000534531.1

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

GnomAD2 exomes AF: 0.00898 AC: 1857 AN: 206882 AF XY: 0.00673

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 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

African (AFR) AF: 0.127 AC: 4210 AN: 33108

American (AMR) AF: 0.00654 AC: 267 AN: 40844

Ashkenazi Jewish (ASJ) AF: 0.00117 AC: 30 AN: 25578

East Asian (EAS) AF: 0.0000258 AC: 1 AN: 38734

South Asian (SAS) AF: 0.000227 AC: 19 AN: 83840

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48038

Middle Eastern (MID) AF: 0.00482 AC: 23 AN: 4768

European-Non Finnish (NFE) AF: 0.000322 AC: 355 AN: 1102314

Other (OTH) AF: 0.00830 AC: 494 AN: 59498

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

African (AFR) AF: 0.125 AC: 5195 AN: 41528

American (AMR) AF: 0.0121 AC: 185 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00103 AC: 5 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000530 AC: 36 AN: 67988

Other (OTH) AF: 0.0275 AC: 58 AN: 2110

Alfa AF: 0.0138 Hom.: 183

Bravo AF: 0.0403

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Deficiency of galactokinase (3)
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	6.9
DANN	Benign	0.70
PhyloP100		0.64
Mutation Taster		=98/2	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: rs7211385; hg19: chr17-73760144;