rs267600971

Variant names:

• chr6-31972346-G-A
• rs267600971
• ENST00000375333.4:c.265G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000375333.4(STK19):​c.265G>A​(p.Asp89Asn) variant causes a missense 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. 14/22 in silico tools predict 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: STK19 ENST00000375333.4 missense
• Clinical Significance: Likely pathogenic no assertion criteria provided P:2
• Conservation: PhyloP100: 1.47
• Publications: 31 publications found

Genes affected

STK19 (HGNC:11398): (serine/threonine kinase 19) This gene encodes a serine/threonine kinase which localizes predominantly to the nucleus. Its specific function is unknown; it is possible that phosphorylation of this protein is involved in transcriptional regulation. This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6 and expresses two transcript variants. [provided by RefSeq, Jul 2008]

DXO (HGNC:2992): (decapping exoribonuclease) This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. The function of its protein product is unknown, but its ubiquitous expression and conservation in both simple and complex eukaryotes suggests that this may be a housekeeping gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.114197046).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DXO	NM_005510.4	c.-424C>T		upstream_gene_variant		ENST00000337523.10	NP_005501.2
WHR1	NM_004197.2	c.-66G>A		upstream_gene_variant		ENST00000685781.1	NP_004188.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DXO	ENST00000337523.10	c.-424C>T		upstream_gene_variant		1	NM_005510.4	ENSP00000337759.5
STK19	ENST00000685781.1	c.-66G>A		upstream_gene_variant			NM_004197.2	ENSP00000509445.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

Submissions by phenotype

Squamous cell carcinoma of the skin Pathogenic:1

May 31, 2016

Database of Curated Mutations (DoCM)

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Malignant melanoma of skin Pathogenic:1

May 31, 2016

Database of Curated Mutations (DoCM)

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0030	.;.;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.62	T;.;.
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	.;L;L
PhyloP100		1.5
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.7	D;N;N
REVEL	Benign	0.043
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;T;T
Polyphen		0.012, 0.0070	.;B;B
Vest4		0.098
MutPred		0.11		Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);
MVP		0.30
MPC		0.60
ClinPred		0.92	D
GERP RS		3.8
PromoterAI		-0.13	Neutral
Varity_R		0.10
gMVP		0.097
Mutation Taster		=90/10	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs267600971; hg19: chr6-31940123; COSMIC: COSV61712753; COSMIC: COSV61712753;