Variant 6-31972415-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004197.2(STK19):c.4A>G(p.Ser2Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,612,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

STK19
NM_004197.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.27

Variant links:

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]

STK19 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12246972).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
STK19	NM_004197.2 linkuse as main transcript	c.4A>G	p.Ser2Gly	missense_variant	1/7	ENST00000685781.1
STK19	NM_032454.1 linkuse as main transcript	c.334A>G	p.Ser112Gly	missense_variant	2/8
STK19	NR_026717.1 linkuse as main transcript	n.647A>G		non_coding_transcript_exon_variant	2/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK19	ENST00000685781.1 linkuse as main transcript	c.4A>G	p.Ser2Gly	missense_variant	1/7		NM_004197.2	P4	P49842-4

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000526

AC:

AN:

247040

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134618

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000319

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000903

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1460752

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726690

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000335

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152080

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

ExAC

AF:

0.0000334

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 26, 2022

The c.334A>G (p.S112G) alteration is located in exon 2 (coding exon 2) of the STK19 gene. This alteration results from a A to G substitution at nucleotide position 334, causing the serine (S) at amino acid position 112 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.42

Cadd

Uncertain

Dann

Uncertain

0.98

Eigen

Benign

-0.080

Eigen_PC

Benign

-0.0049

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.46

T;.;.

M_CAP

Benign

0.031

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.99

N;N

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.2

D;N;N

REVEL

Benign

0.033

Sift

Benign

0.042

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.76, 0.24

.;P;B

Vest4

0.33, 0.31

MutPred

0.21

Loss of phosphorylation at S112 (P = 0.0183);Loss of phosphorylation at S112 (P = 0.0183);Loss of phosphorylation at S112 (P = 0.0183);

MVP

0.57

MPC

0.79

ClinPred

0.16

GERP RS

4.5

Varity_R

0.12

gMVP

0.18

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over