rs76160162

Variant names:

• chr17-75758360-C-T
• rs76160162
• NM_000154.2:c.957G>A

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.957G>A​(p.Glu319Glu) 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:3
• Conservation: PhyloP100: 1.06
• Publications: 0 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=-0.47).
• BP6: Variant 17-75758360-C-T is Benign according to our data. Variant chr17-75758360-C-T is described in ClinVar as Benign. ClinVar VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 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.957G>A	p.Glu319Glu	synonymous	Exon 7 of 8	NP_000145.1	P51570
	GALK1	NM_001381985.1		c.957G>A	p.Glu319Glu	synonymous	Exon 7 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.957G>A	p.Glu319Glu	synonymous	Exon 7 of 8	ENSP00000465930.1	P51570
	GALK1	ENST00000864472.1		c.1053G>A	p.Glu351Glu	synonymous	Exon 8 of 9	ENSP00000534531.1
	GALK1	ENST00000864469.1		c.1050G>A	p.Glu350Glu	synonymous	Exon 8 of 9	ENSP00000534528.1

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

GnomAD2 exomes AF: 0.000895 AC: 189 AN: 211200 AF XY: 0.000620

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 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

African (AFR) AF: 0.0153 AC: 508 AN: 33230

American (AMR) AF: 0.000778 AC: 32 AN: 41114

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25622

East Asian (EAS) AF: 0.00 AC: 0 AN: 38832

South Asian (SAS) AF: 0.0000120 AC: 1 AN: 83324

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50412

Middle Eastern (MID) AF: 0.000522 AC: 3 AN: 5750

European-Non Finnish (NFE) AF: 0.00000272 AC: 3 AN: 1102310

Other (OTH) AF: 0.000990 AC: 59 AN: 59606

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

African (AFR) AF: 0.0129 AC: 536 AN: 41592

American (AMR) AF: 0.00163 AC: 25 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68024

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00177 Hom.: 0

Bravo AF: 0.00445

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	11
DANN	Benign	0.87
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs76160162; hg19: chr17-73754441; COSMIC: COSV99564003; COSMIC: COSV99564003;