15-49217303-C-G

Variant names:

• chr15-49217303-C-G
• rs371025596
• NM_002044.4:c.256C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001352047.1(GALK2):​c.-277C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GALK2 NM_001352047.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.59
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27592042).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001352047.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALK2	NM_002044.4	MANE Select	c.256C>G	p.Pro86Ala	missense	Exon 3 of 10	NP_002035.1	Q01415-1
	GALK2	NM_001352047.1		c.-277C>G		5_prime_UTR_premature_start_codon_gain	Exon 3 of 12	NP_001338976.1
	GALK2	NM_001352048.2		c.-277C>G		5_prime_UTR_premature_start_codon_gain	Exon 3 of 12	NP_001338977.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALK2	ENST00000560031.6	TSL:1 MANE Select	c.256C>G	p.Pro86Ala	missense	Exon 3 of 10	ENSP00000453129.1	Q01415-1
	GALK2	ENST00000327171.7	TSL:1	c.223C>G	p.Pro75Ala	missense	Exon 3 of 10	ENSP00000316632.3	Q01415-2
	GALK2	ENST00000968619.1		c.256C>G	p.Pro86Ala	missense	Exon 3 of 10	ENSP00000638678.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Uncertain	0.061	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.067
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.57	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		1.6
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.31
Sift	Benign	0.23	T
Sift4G	Benign	0.22	T
Polyphen		0.0020	B
Vest4		0.54
MutPred		0.40		Loss of sheet (P = 0.1158)
MVP		0.95
MPC		0.040
ClinPred		0.82	D
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs371025596; hg19: chr15-49509500;