rs200502537

chr17-75758228-G-Achr17-75758228-G-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_000154.2(GALK1):c.1089C>T(p.His363=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000206 in 1,604,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: GALK1 NM_000154.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.90

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 Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 17-75758228-G-A is Benign according to our data. Variant chr17-75758228-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 459628.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.89 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALK1	NM_000154.2	c.1089C>T	p.His363=	synonymous_variant	7/8	ENST00000588479.6
GALK1	NM_001381985.1	c.1089C>T	p.His363=	synonymous_variant	7/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALK1	ENST00000588479.6	c.1089C>T	p.His363=	synonymous_variant	7/8	1	NM_000154.2	P1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152230 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000619 AC: 14 AN: 226136 Hom.: 0 AF XY: 0.0000647 AC XY: 8 AN XY: 123734

Gnomad AFR exome AF: 0.0000732

Gnomad AMR exome AF: 0.000123

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000117

Gnomad SAS exome AF: 0.000206

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000100

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000200 AC: 29 AN: 1452396 Hom.: 0 Cov.: 34 AF XY: 0.0000222 AC XY: 16 AN XY: 721940

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000924

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000127

Gnomad4 SAS exome AF: 0.0000821

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000902

Gnomad4 OTH exome AF: 0.0000500

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152348 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74498

Gnomad4 AFR AF: 0.0000721

Gnomad4 AMR AF: 0.0000653

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000189

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Deficiency of galactokinase Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Sep 27, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.073
Dann	Benign	0.91
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs200502537; hg19: chr17-73754309; COSMIC: COSV52332845; COSMIC: COSV52332845;