chr15-49235888-A-C

Variant summary

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

The NM_002044.4(GALK2):ā€‹c.304A>Cā€‹(p.Lys102Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,454 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000041 ( 0 hom. )

Consequence

GALK2
NM_002044.4 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.60
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=0.19868386).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GALK2NM_002044.4 linkuse as main transcriptc.304A>C p.Lys102Gln missense_variant 4/10 ENST00000560031.6 NP_002035.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GALK2ENST00000560031.6 linkuse as main transcriptc.304A>C p.Lys102Gln missense_variant 4/101 NM_002044.4 ENSP00000453129 P1Q01415-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000411
AC:
6
AN:
1461454
Hom.:
0
Cov.:
29
AF XY:
0.00000413
AC XY:
3
AN XY:
727046
show subpopulations
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:
0.00000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

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 06, 2023The c.304A>C (p.K102Q) alteration is located in exon 4 (coding exon 4) of the GALK2 gene. This alteration results from a A to C substitution at nucleotide position 304, causing the lysine (K) at amino acid position 102 to be replaced by a glutamine (Q). 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
0.098
BayesDel_addAF
Benign
-0.035
T
BayesDel_noAF
Benign
-0.29
CADD
Benign
18
DANN
Benign
0.83
DEOGEN2
Benign
0.066
.;T;T;T;.;T;T;T
Eigen
Benign
-0.35
Eigen_PC
Benign
-0.23
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Uncertain
0.89
D;D;D;.;D;.;D;D
M_CAP
Benign
0.076
D
MetaRNN
Benign
0.20
T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.50
T
MutationAssessor
Benign
1.3
.;.;L;.;.;.;.;.
MutationTaster
Benign
0.99
D;D;D;D;D;D
PrimateAI
Uncertain
0.48
T
PROVEAN
Benign
-0.64
N;N;N;N;N;N;N;N
REVEL
Uncertain
0.30
Sift
Benign
0.50
T;T;T;T;T;T;T;T
Sift4G
Benign
0.56
T;T;T;T;T;T;T;T
Polyphen
0.0
.;.;B;.;.;.;.;.
Vest4
0.24
MutPred
0.42
.;.;Loss of ubiquitination at K102 (P = 0.0118);.;.;.;.;.;
MVP
0.82
MPC
0.041
ClinPred
0.41
T
GERP RS
1.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.20
gMVP
0.59

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: chr15-49528085; API