chr15-49283704-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_002044.4(GALK2):​c.742C>T​(p.Arg248Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000415 in 1,613,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000041 ( 0 hom. )

Consequence

GALK2
NM_002044.4 missense

Scores

10
8
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.64
Variant links:
Genes affected
GALK2 (HGNC:4119): (galactokinase 2) This gene encodes a highly efficient N-acetylgalactosamine (GalNAc) kinase, which has galactokinase activity when galactose is present at high concentrations. The encoded protein is a member of the GHMP kinase family. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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, 0.925

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GALK2NM_002044.4 linkuse as main transcriptc.742C>T p.Arg248Trp missense_variant 7/10 ENST00000560031.6 NP_002035.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GALK2ENST00000560031.6 linkuse as main transcriptc.742C>T p.Arg248Trp missense_variant 7/101 NM_002044.4 ENSP00000453129 P1Q01415-1

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152064
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000637
AC:
16
AN:
251198
Hom.:
0
AF XY:
0.0000589
AC XY:
8
AN XY:
135750
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000655
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000968
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000411
AC:
60
AN:
1461610
Hom.:
0
Cov.:
30
AF XY:
0.0000413
AC XY:
30
AN XY:
727104
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000812
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152064
Hom.:
0
Cov.:
32
AF XY:
0.0000539
AC XY:
4
AN XY:
74272
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000138
Hom.:
0
Bravo
AF:
0.0000718
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000494
AC:
6
EpiCase
AF:
0.000164
EpiControl
AF:
0.000119

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 04, 2023The c.742C>T (p.R248W) alteration is located in exon 7 (coding exon 7) of the GALK2 gene. This alteration results from a C to T substitution at nucleotide position 742, causing the arginine (R) at amino acid position 248 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.37
BayesDel_addAF
Pathogenic
0.31
D
BayesDel_noAF
Pathogenic
0.41
CADD
Pathogenic
31
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.57
.;D;T;T;T;T
Eigen
Uncertain
0.66
Eigen_PC
Uncertain
0.60
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.95
D;D;.;.;D;D
M_CAP
Uncertain
0.22
D
MetaRNN
Pathogenic
0.93
D;D;D;D;D;D
MetaSVM
Pathogenic
0.90
D
MutationAssessor
Pathogenic
3.6
.;H;.;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D
PrimateAI
Uncertain
0.72
T
PROVEAN
Pathogenic
-6.5
D;D;D;D;D;D
REVEL
Pathogenic
0.89
Sift
Pathogenic
0.0
D;D;D;D;D;D
Sift4G
Pathogenic
0.0010
D;D;D;D;D;D
Polyphen
1.0
.;D;.;.;.;.
Vest4
0.76
MVP
0.98
MPC
0.29
ClinPred
0.99
D
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.84
gMVP
0.80

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs370443921; hg19: chr15-49575901; API