NM_002044.4:c.422G>T

Variant names:

• chr15-49239285-G-T
• rs779555164
• NM_002044.4:c.422G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_002044.4(GALK2):​c.422G>T​(p.Ser141Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S141N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GALK2 NM_002044.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.25
• Publications: 0 publications found

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]

ENSG00000305168 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.87

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALK2	NM_002044.4	c.422G>T	p.Ser141Ile	missense_variant	Exon 5 of 10	ENST00000560031.6	NP_002035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALK2	ENST00000560031.6	c.422G>T	p.Ser141Ile	missense_variant	Exon 5 of 10	1	NM_002044.4	ENSP00000453129.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461846 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727224

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111980

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.83	.;D;D;D;D;D;D
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D;D;.;.;D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.87	D;D;D;D;D;D;D
MetaSVM	Uncertain	0.66	D
MutationAssessor	Pathogenic	3.0	.;.;M;.;.;.;.
PhyloP100		7.3
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-4.9	D;D;D;D;D;D;D
REVEL	Pathogenic	0.81
Sift	Uncertain	0.0030	D;D;D;D;D;D;D
Sift4G	Uncertain	0.016	D;D;D;D;D;D;D
Polyphen		1.0	.;.;D;.;.;.;.
Vest4		0.64
MutPred		0.67		.;.;Loss of disorder (P = 0.0088);.;.;.;.;
MVP		0.98
MPC		0.30
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.98
gMVP		0.86
Mutation Taster		=6/94	disease causing

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

Other links and lift over

dbSNP: rs779555164; hg19: chr15-49531482;