rs753571180

Variant names:

• chr17-75758552-C-G
• NM_000154.2:c.841G>C

Your query was ambiguous. Multiple possible variants found:

• chr17-75758552-C-G
• chr17-75758552-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_000154.2(GALK1):​c.841G>C​(p.Val281Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,443,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: GALK1 NM_000154.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.38

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.912

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALK1	NM_000154.2	c.841G>C	p.Val281Leu	missense_variant	Exon 6 of 8	ENST00000588479.6	NP_000145.1
GALK1	NM_001381985.1	c.841G>C	p.Val281Leu	missense_variant	Exon 6 of 9		NP_001368914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALK1	ENST00000588479.6	c.841G>C	p.Val281Leu	missense_variant	Exon 6 of 8	1	NM_000154.2	ENSP00000465930.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1443794 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 717936

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.02e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.70	D;.;D
Eigen	Pathogenic	0.74
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	1.0	.;D;D
M_CAP	Pathogenic	0.34	D
MetaRNN	Pathogenic	0.91	D;D;D
MetaSVM	Pathogenic	0.86	D
MutationAssessor	Pathogenic	4.0	H;.;H
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-2.6	D;.;.
REVEL	Pathogenic	0.80
Sift	Uncertain	0.010	D;.;.
Sift4G	Uncertain	0.020	D;D;D
Polyphen		0.98	D;.;D
Vest4		0.84
MutPred		0.72		Gain of disorder (P = 0.2287);.;Gain of disorder (P = 0.2287);
MVP		0.91
MPC		0.64
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.84
gMVP		0.86

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-73754633;