chr17-75763386-C-T

Variant names:

• chr17-75763386-C-T
• rs1555748630
• NM_000154.2:c.409G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000154.2(GALK1):​c.409G>A​(p.Gly137Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,460,932 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GALK1 NM_000154.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.85

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALK1	NM_000154.2	c.409G>A	p.Gly137Ser	missense_variant	Exon 3 of 8	ENST00000588479.6	NP_000145.1
GALK1	NM_001381985.1	c.409G>A	p.Gly137Ser	missense_variant	Exon 3 of 9		NP_001368914.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALK1	ENST00000588479.6	c.409G>A	p.Gly137Ser	missense_variant	Exon 3 of 8	1	NM_000154.2	ENSP00000465930.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1460932 Hom.: 0 Cov.: 37 AF XY: 0.00000138 AC XY: 1 AN XY: 726748

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.061	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.80	D;D
Eigen	Benign	0.10
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.88	.;D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.58	D;D
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Benign	0.19	N;N
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-2.9	D;.
REVEL	Uncertain	0.44
Sift	Benign	0.18	T;.
Sift4G	Benign	0.26	T;T
Polyphen		0.065	B;B
Vest4		0.49
MutPred		0.64		Gain of glycosylation at G137 (P = 0.004);Gain of glycosylation at G137 (P = 0.004);
MVP		0.86
MPC		0.28
ClinPred		0.93	D
GERP RS		5.2
Varity_R		0.81
gMVP		0.84

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

LitVar

Other links and lift over

dbSNP: rs1555748630; hg19: chr17-73759467;