Variant 6-31972492-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004197.2(STK19):c.81T>G(p.Asp27Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000999 in 1,612,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

STK19
NM_004197.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.118

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:

STK19 (HGNC:):

STK19 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.055922776).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK19	NM_004197.2 linkuse as main transcript	c.81T>G	p.Asp27Glu	missense_variant	1/7	ENST00000685781.1	NP_004188.2	P49842-4A0A1U9X8L3
STK19	NM_032454.1 linkuse as main transcript	c.411T>G	p.Asp137Glu	missense_variant	2/8		NP_115830.1	P49842-1
STK19	NR_026717.1 linkuse as main transcript	n.724T>G		non_coding_transcript_exon_variant	2/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK19	ENST00000685781.1 linkuse as main transcript	c.81T>G	p.Asp27Glu	missense_variant	1/7		NM_004197.2	ENSP00000509445.1		P49842-4

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000930

AC:

AN:

247196

Hom.:

AF XY:

0.0000965

AC XY:

AN XY:

134696

show subpopulations

Gnomad AFR exome

AF:

0.000132

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000934

Gnomad NFE exome

AF:

0.000144

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000100

AC:

146

AN:

1460008

Hom.:

Cov.:

AF XY:

0.000106

AC XY:

AN XY:

726196

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000959

Gnomad4 NFE exome

AF:

0.000109

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.0000986

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000975

Hom.:

Bravo

AF:

0.000193

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000993

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

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 17, 2024

The c.411T>G (p.D137E) alteration is located in exon 2 (coding exon 2) of the STK19 gene. This alteration results from a T to G substitution at nucleotide position 411, causing the aspartic acid (D) at amino acid position 137 to be replaced by a glutamic acid (E). 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

0.13

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.62

CADD

Benign

7.9

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0035

.;T

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.020

M_CAP

Benign

0.012

MetaRNN

Benign

0.056

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.81

L;L

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.0080

Sift

Benign

0.092

T;T

Sift4G

Benign

0.49

T;T

Polyphen

0.11

B;B

Vest4

0.18

MutPred

0.41

Loss of MoRF binding (P = 0.1246);Loss of MoRF binding (P = 0.1246);

MVP

0.13

MPC

0.50

ClinPred

0.030

GERP RS

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.047

gMVP

0.094

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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