6-36521808-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_007271.4(STK38):​c.316G>T​(p.Val106Phe) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V106L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 32)
  • Exomes 𝑓: 0.013 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: STK38 NM_007271.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91
• Publications: 9 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0028530955).

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>T	p.Val106Phe	missense	Exon 5 of 14	NP_009202.1	Q15208
	STK38	NM_001305102.2		c.316G>T	p.Val106Phe	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>T	p.Val106Phe	missense	Exon 5 of 14	ENSP00000229812.7	Q15208
	STK38	ENST00000869137.1		c.316G>T	p.Val106Phe	missense	Exon 5 of 15	ENSP00000539196.1
	STK38	ENST00000850860.1		c.316G>T	p.Val106Phe	missense	Exon 5 of 14	ENSP00000520947.1

Frequencies

GnomAD3 genomes AF: 0.0000724 AC: 11 AN: 151876 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000148

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.123 AC: 26668 AN: 216268 AF XY: 0.125

Gnomad AFR exome AF: 0.201

Gnomad AMR exome AF: 0.121

Gnomad ASJ exome AF: 0.0542

Gnomad EAS exome AF: 0.160

Gnomad FIN exome AF: 0.163

Gnomad NFE exome AF: 0.121

Gnomad OTH exome AF: 0.0719

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0132 AC: 18875 AN: 1435134 Hom.: 0 Cov.: 30 AF XY: 0.0151 AC XY: 10735 AN XY: 711496

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0274 AC: 911 AN: 33212

American (AMR) AF: 0.0924 AC: 3938 AN: 42620

Ashkenazi Jewish (ASJ) AF: 0.0205 AC: 509 AN: 24842

East Asian (EAS) AF: 0.0494 AC: 1944 AN: 39392

South Asian (SAS) AF: 0.0266 AC: 2152 AN: 80846

European-Finnish (FIN) AF: 0.0395 AC: 1841 AN: 46564

Middle Eastern (MID) AF: 0.00374 AC: 21 AN: 5614

European-Non Finnish (NFE) AF: 0.00635 AC: 7001 AN: 1102552

Other (OTH) AF: 0.00938 AC: 558 AN: 59492

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000724 AC: 11 AN: 151876 Hom.: 0 Cov.: 32 AF XY: 0.0000540 AC XY: 4 AN XY: 74140

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41432

American (AMR) AF: 0.00 AC: 0 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.000289 AC: 1 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000148 AC: 10 AN: 67792

Other (OTH) AF: 0.00 AC: 0 AN: 2090

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00122 Hom.: 3

ExAC AF: 0.231 AC: 27288

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T
Eigen	Pathogenic	0.96
Eigen_PC	Pathogenic	0.91
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D
MetaRNN	Benign	0.0029	T
MetaSVM	Benign	-0.42	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		7.9
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-4.0	D
REVEL	Uncertain	0.50
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.36
MPC		1.6
ClinPred		0.021	T
GERP RS		5.5
Varity_R		0.99
gMVP		0.87
Mutation Taster		=0/100	polymorphism (auto)

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; COSMIC: COSV57707394; COSMIC: COSV57707394;