chr15-49170348-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002044.4(GALK2):​c.26G>A​(p.Arg9His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 152,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

GALK2
NM_002044.4 missense

Scores

2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.831
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08600506).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GALK2NM_002044.4 linkuse as main transcriptc.26G>A p.Arg9His missense_variant 1/10 ENST00000560031.6 NP_002035.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GALK2ENST00000560031.6 linkuse as main transcriptc.26G>A p.Arg9His missense_variant 1/101 NM_002044.4 ENSP00000453129 P1Q01415-1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152202
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1440188
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
713740
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152202
Hom.:
0
Cov.:
31
AF XY:
0.0000404
AC XY:
3
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.0000965
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113

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 GeneticsJan 19, 2024The c.26G>A (p.R9H) alteration is located in exon 1 (coding exon 1) of the GALK2 gene. This alteration results from a G to A substitution at nucleotide position 26, causing the arginine (R) at amino acid position 9 to be replaced by a histidine (H). 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
Benign
0.13
BayesDel_addAF
Uncertain
0.038
T
BayesDel_noAF
Benign
-0.18
CADD
Benign
15
DANN
Uncertain
1.0
DEOGEN2
Benign
0.077
T
Eigen
Benign
-0.71
Eigen_PC
Benign
-0.65
FATHMM_MKL
Benign
0.58
D
LIST_S2
Benign
0.73
T
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.086
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.0
L
MutationTaster
Benign
1.0
N;N;N;N;N
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-0.70
N
Sift
Benign
0.19
T
Sift4G
Benign
0.16
T
Polyphen
0.0
B
Vest4
0.13
MutPred
0.22
Loss of loop (P = 0.0603);
MVP
0.71
MPC
0.045
ClinPred
0.25
T
GERP RS
3.0
Varity_R
0.083
gMVP
0.74

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs915829029; hg19: chr15-49462545; API