Variant chr7-43583380-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_004760.3(STK17A):c.137T>C(p.Ile46Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000103 in 1,448,126 control chromosomes in the GnomAD database, including 2 homozygotes. 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 0.000086 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00010 ( 2 hom. )

Consequence

STK17A
NM_004760.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.84

Variant links:

Genes affected

STK17A (HGNC:11395): (serine/threonine kinase 17a) This gene is a member of the DAP kinase-related apoptosis-inducing protein kinase family and encodes an autophosphorylated nuclear protein with a protein kinase domain. The protein has apoptosis-inducing activity. [provided by RefSeq, Jul 2008]

STK17A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3854875).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK17A	NM_004760.3 linkuse as main transcript	c.137T>C	p.Ile46Thr	missense_variant	1/7	ENST00000319357.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
STK17A	ENST00000319357.6 linkuse as main transcript	c.137T>C	p.Ile46Thr	missense_variant	1/7	1	NM_004760.3	P1
STK17A	ENST00000648544.1 linkuse as main transcript	c.137T>C	p.Ile46Thr	missense_variant, NMD_transcript_variant	1/9
STK17A	ENST00000462448.1 linkuse as main transcript	n.204+419T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000857

AC:

AN:

151638

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000191

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000541

AC:

AN:

73900

Hom.:

AF XY:

0.0000474

AC XY:

AN XY:

42230

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000826

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000809

Gnomad NFE exome

AF:

0.0000815

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000105

AC:

136

AN:

1296378

Hom.:

Cov.:

AF XY:

0.000105

AC XY:

AN XY:

638116

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000446

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000224

Gnomad4 NFE exome

AF:

0.000126

Gnomad4 OTH exome

AF:

0.0000755

GnomAD4 genome

AF:

0.0000857

AC:

AN:

151748

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74144

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000139

Hom.:

Bravo

AF:

0.0000642

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

May 16, 2023

The c.137T>C (p.I46T) alteration is located in exon 1 (coding exon 1) of the STK17A gene. This alteration results from a T to C substitution at nucleotide position 137, causing the isoleucine (I) at amino acid position 46 to be replaced by a threonine (T). 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

Uncertain

0.51

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.025

Eigen

Benign

0.12

Eigen_PC

Benign

0.086

FATHMM_MKL

Benign

0.60

M_CAP

Pathogenic

0.56

MetaRNN

Benign

0.39

MetaSVM

Benign

-0.65

MutationAssessor

Benign

1.8

MutationTaster

Benign

0.77

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

-0.90

REVEL

Benign

0.21

Sift

Benign

0.37

Sift4G

Benign

0.26

Polyphen

1.0

Vest4

0.38

MVP

0.79

MPC

0.55

ClinPred

0.16

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.095

gMVP

0.54

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