rs73997615

Variant names:

• chr17-75758116-G-A
• rs73997615
• NM_000154.2:c.1119C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-75758116-G-A
• chr17-75758116-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_000154.2(GALK1):​c.1119C>T​(p.Gly373Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 1,612,686 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0023 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0013 (9 hom.)
• Consequence: GALK1 NM_000154.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -3.90
• Publications: 2 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=-0.88).
• BP6: Variant 17-75758116-G-A is Benign according to our data. Variant chr17-75758116-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 459629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.9 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00232 (353/152320) while in subpopulation AMR AF = 0.00438 (67/15310). AF 95% confidence interval is 0.00354. There are 0 homozygotes in GnomAd4. There are 178 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 9 AR gene

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.1119C>T	p.Gly373Gly	synonymous	Exon 8 of 8	NP_000145.1	P51570
	GALK1	NM_001381985.1		c.1119C>T	p.Gly373Gly	synonymous	Exon 8 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.1119C>T	p.Gly373Gly	synonymous	Exon 8 of 8	ENSP00000465930.1	P51570
	GALK1	ENST00000864472.1		c.1215C>T	p.Gly405Gly	synonymous	Exon 9 of 9	ENSP00000534531.1
	GALK1	ENST00000864469.1		c.1212C>T	p.Gly404Gly	synonymous	Exon 9 of 9	ENSP00000534528.1

Frequencies

GnomAD3 genomes AF: 0.00232 AC: 353 AN: 152202 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00256

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00438

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00118

Gnomad OTH AF: 0.00860

GnomAD2 exomes AF: 0.00213 AC: 527 AN: 246894 AF XY: 0.00197

Gnomad AFR exome AF: 0.00271

Gnomad AMR exome AF: 0.00441

Gnomad ASJ exome AF: 0.0162

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000467

Gnomad NFE exome AF: 0.00126

Gnomad OTH exome AF: 0.00464

GnomAD4 exome AF: 0.00127 AC: 1860 AN: 1460366 Hom.: 9 Cov.: 32 AF XY: 0.00131 AC XY: 949 AN XY: 726466

African (AFR) AF: 0.00290 AC: 97 AN: 33476

American (AMR) AF: 0.00456 AC: 204 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0169 AC: 441 AN: 26126

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39694

South Asian (SAS) AF: 0.000267 AC: 23 AN: 86246

European-Finnish (FIN) AF: 0.0000384 AC: 2 AN: 52060

Middle Eastern (MID) AF: 0.00798 AC: 46 AN: 5766

European-Non Finnish (NFE) AF: 0.000780 AC: 867 AN: 1111920

Other (OTH) AF: 0.00295 AC: 178 AN: 60360

GnomAD4 genome AF: 0.00232 AC: 353 AN: 152320 Hom.: 0 Cov.: 33 AF XY: 0.00239 AC XY: 178 AN XY: 74476

African (AFR) AF: 0.00255 AC: 106 AN: 41570

American (AMR) AF: 0.00438 AC: 67 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0225 AC: 78 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10628

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00118 AC: 80 AN: 68008

Other (OTH) AF: 0.00851 AC: 18 AN: 2114

Alfa AF: 0.00287 Hom.: 2

Bravo AF: 0.00304

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00174

EpiControl AF: 0.00166

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Deficiency of galactokinase (3)
-	-	2	not provided (2)
-	-	1	Junctional epidermolysis bullosa with pyloric atresia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.27
DANN	Benign	0.55
PhyloP100		-3.9
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs73997615; hg19: chr17-73754197; COSMIC: COSV52325976; COSMIC: COSV52325976;