chr15-49170336-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002044.4(GALK2):ā€‹c.14G>Cā€‹(p.Ser5Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000417 in 1,438,500 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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: 31)
Exomes š‘“: 0.0000042 ( 0 hom. )

Consequence

GALK2
NM_002044.4 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.21
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.05309519).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GALK2NM_002044.4 linkuse as main transcriptc.14G>C p.Ser5Thr 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.14G>C p.Ser5Thr missense_variant 1/101 NM_002044.4 ENSP00000453129 P1Q01415-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000956
AC:
2
AN:
209224
Hom.:
0
AF XY:
0.00000889
AC XY:
1
AN XY:
112448
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000641
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000108
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000417
AC:
6
AN:
1438500
Hom.:
0
Cov.:
30
AF XY:
0.00000561
AC XY:
4
AN XY:
712652
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000257
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000454
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.00000756
ExAC
AF:
0.00000831
AC:
1

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 GeneticsMay 02, 2024The c.14G>C (p.S5T) alteration is located in exon 1 (coding exon 1) of the GALK2 gene. This alteration results from a G to C substitution at nucleotide position 14, causing the serine (S) at amino acid position 5 to be replaced by a threonine (T). 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
0.079
BayesDel_addAF
Benign
-0.066
T
BayesDel_noAF
Benign
-0.33
CADD
Benign
15
DANN
Benign
0.61
DEOGEN2
Benign
0.062
T
Eigen
Benign
-0.66
Eigen_PC
Benign
-0.52
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.53
T
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.053
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.34
N
MutationTaster
Benign
1.0
D;D;D;D;N
PrimateAI
Benign
0.37
T
PROVEAN
Benign
0.43
N
Sift
Benign
0.55
T
Sift4G
Benign
0.58
T
Polyphen
0.0010
B
Vest4
0.11
MutPred
0.17
Loss of phosphorylation at S5 (P = 0.0797);
MVP
0.83
MPC
0.037
ClinPred
0.061
T
GERP RS
3.0
Varity_R
0.079
gMVP
0.68

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

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

Other links and lift over

dbSNP: rs760667559; hg19: chr15-49462533; API