chr6-36521808-C-G

Variant names:

• chr6-36521808-C-G
• rs200294413
• NM_007271.4:c.316G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_007271.4(STK38):​c.316G>C​(p.Val106Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V106F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: STK38 NM_007271.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91
• Publications: 0 publications found

Genes affected

STK38 (HGNC:17847): (serine/threonine kinase 38) This gene encodes a member of the AGC serine/threonine kinase family of proteins. The kinase activity of this protein is regulated by autophosphorylation and phosphorylation by other upstream kinases. This protein has been shown to function in the cell cycle and apoptosis. This protein has also been found to regulate the protein stability and transcriptional activity of the MYC oncogene. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.814

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007271.4. 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
	STK38	NM_007271.4	MANE Select	c.316G>C	p.Val106Leu	missense	Exon 5 of 14	NP_009202.1	Q15208
	STK38	NM_001305102.2		c.316G>C	p.Val106Leu	missense	Exon 5 of 14	NP_001292031.1	Q15208

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK38	ENST00000229812.8	TSL:1 MANE Select	c.316G>C	p.Val106Leu	missense	Exon 5 of 14	ENSP00000229812.7	Q15208
	STK38	ENST00000869137.1		c.316G>C	p.Val106Leu	missense	Exon 5 of 15	ENSP00000539196.1
	STK38	ENST00000850860.1		c.316G>C	p.Val106Leu	missense	Exon 5 of 14	ENSP00000520947.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Benign	-0.0051	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.015	T
MetaRNN	Pathogenic	0.81	D
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		7.9
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.37
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.012	D
Polyphen		0.95	P
Vest4		0.77
MutPred		0.78		Loss of MoRF binding (P = 0.1029)
MVP		0.45
MPC		0.94
ClinPred		0.98	D
GERP RS		5.5
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.95
gMVP		0.75
Mutation Taster		=19/81	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: rs200294413; hg19: chr6-36489585;