chr15-49201181-A-G

Variant summary

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

The NM_002044.4(GALK2):ā€‹c.73A>Gā€‹(p.Met25Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000256 in 1,602,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00016 ( 0 hom., cov: 32)
Exomes š‘“: 0.000011 ( 0 hom. )

Consequence

GALK2
NM_002044.4 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.14
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=0.13722521).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GALK2NM_002044.4 linkuse as main transcriptc.73A>G p.Met25Val missense_variant 2/10 ENST00000560031.6 NP_002035.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GALK2ENST00000560031.6 linkuse as main transcriptc.73A>G p.Met25Val missense_variant 2/101 NM_002044.4 ENSP00000453129 P1Q01415-1

Frequencies

GnomAD3 genomes
AF:
0.000164
AC:
25
AN:
152064
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000555
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000398
AC:
10
AN:
250972
Hom.:
0
AF XY:
0.0000295
AC XY:
4
AN XY:
135688
show subpopulations
Gnomad AFR exome
AF:
0.000554
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000110
AC:
16
AN:
1450330
Hom.:
0
Cov.:
28
AF XY:
0.00000830
AC XY:
6
AN XY:
722510
show subpopulations
Gnomad4 AFR exome
AF:
0.000361
Gnomad4 AMR exome
AF:
0.0000224
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:
0.0000500
GnomAD4 genome
AF:
0.000164
AC:
25
AN:
152182
Hom.:
0
Cov.:
32
AF XY:
0.000161
AC XY:
12
AN XY:
74390
show subpopulations
Gnomad4 AFR
AF:
0.000554
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000668
Hom.:
0
Bravo
AF:
0.000159
ESP6500AA
AF:
0.000683
AC:
3
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000494
AC:
6

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 GeneticsFeb 06, 2023The c.73A>G (p.M25V) alteration is located in exon 2 (coding exon 2) of the GALK2 gene. This alteration results from a A to G substitution at nucleotide position 73, causing the methionine (M) at amino acid position 25 to be replaced by a valine (V). 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
0.092
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Uncertain
-0.070
CADD
Benign
19
DANN
Uncertain
0.98
DEOGEN2
Benign
0.082
.;T;T;T;.;T;T;T
Eigen
Benign
-0.32
Eigen_PC
Benign
-0.078
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Uncertain
0.89
D;D;D;.;D;.;D;D
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.090
T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.47
T
MutationAssessor
Benign
-0.18
.;.;N;.;.;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;N;N
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
-1.1
N;N;N;N;N;N;N;N
REVEL
Benign
0.23
Sift
Benign
0.49
T;T;T;T;D;T;D;T
Sift4G
Benign
0.51
T;T;T;T;T;T;T;T
Polyphen
0.0010
.;.;B;.;.;.;.;.
Vest4
0.44
MVP
0.89
MPC
0.041
ClinPred
0.031
T
GERP RS
5.1
Varity_R
0.14
gMVP
0.57

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: rs139521545; hg19: chr15-49493378; API