chr1-45345193-G-A

Position:

chr1-45345193-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_007170.3(TESK2):c.1363C>T(p.Arg455Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0682 in 1,614,134 control chromosomes in the GnomAD database, including 4,320 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R455H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.050 ( 274 hom., cov: 32)

Exomes 𝑓: 0.070 ( 4046 hom. )

Consequence

TESK2
NM_007170.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.28

Variant links:

Genes affected

TESK2 (HGNC:11732): (testis associated actin remodelling kinase 2) This gene product is a serine/threonine protein kinase that contains an N-terminal protein kinase domain that is structurally similar to the kinase domains of testis-specific protein kinase-1 and the LIM motif-containing protein kinases (LIMKs). Its overall structure is most related to the former, indicating that it belongs to the TESK subgroup of the LIMK/TESK family of protein kinases. This gene is predominantly expressed in testis and prostate. The developmental expression pattern of the rat gene in testis suggests an important role for this gene in meitoic stages and/or early stages of spermiogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

TESK2 links:

ENSG00000288208 (HGNC:):

ENSG00000288208 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024671257).

BP6

Variant 1-45345193-G-A is Benign according to our data. Variant chr1-45345193-G-A is described in ClinVar as [Benign]. Clinvar id is 1264064.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TESK2	NM_007170.3 link	c.1363C>T	p.Arg455Cys	missense_variant	11/11	ENST00000372086.4	NP_009101.2	Q96S53-1
TESK2	NM_001320800.2 link	c.1114C>T	p.Arg372Cys	missense_variant	10/10		NP_001307729.1	Q96S53B4DFN2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TESK2	ENST00000372086.4 link	c.1363C>T	p.Arg455Cys	missense_variant	11/11	1	NM_007170.3	ENSP00000361158.3	Q96S53-1
TESK2	ENST00000372084.5 link	c.1276C>T	p.Arg426Cys	missense_variant	9/9	1		ENSP00000361156.1	Q96S53-3
ENSG00000288208	ENST00000671898.1 link	n.540+10110C>T		intron_variant				ENSP00000499896.1	A0A5F9ZGZ0
TESK2	ENST00000486676.5 link	n.1710C>T		non_coding_transcript_exon_variant	10/10	5

Frequencies

GnomAD3 genomes

AF:

0.0501

AC:

7618

AN:

152180

Hom.:

274

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0120

Gnomad AMI

AF:

0.0385

Gnomad AMR

AF:

0.0344

Gnomad ASJ

AF:

0.0418

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0317

Gnomad FIN

AF:

0.0768

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0786

Gnomad OTH

AF:

0.0421

GnomAD3 exomes

AF:

0.0517

AC:

12899

AN:

249306

Hom.:

448

AF XY:

0.0527

AC XY:

7126

AN XY:

135300

show subpopulations

Gnomad AFR exome

AF:

0.0114

Gnomad AMR exome

AF:

0.0203

Gnomad ASJ exome

AF:

0.0432

Gnomad EAS exome

AF:

0.000222

Gnomad SAS exome

AF:

0.0332

Gnomad FIN exome

AF:

0.0767

Gnomad NFE exome

AF:

0.0760

Gnomad OTH exome

AF:

0.0537

GnomAD4 exome

AF:

0.0701

AC:

102537

AN:

1461836

Hom.:

4046

Cov.:

AF XY:

0.0693

AC XY:

50372

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.0106

Gnomad4 AMR exome

AF:

0.0224

Gnomad4 ASJ exome

AF:

0.0429

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0341

Gnomad4 FIN exome

AF:

0.0766

Gnomad4 NFE exome

AF:

0.0801

Gnomad4 OTH exome

AF:

0.0642

GnomAD4 genome

AF:

0.0500

AC:

7618

AN:

152298

Hom.:

274

Cov.:

AF XY:

0.0491

AC XY:

3653

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0120

Gnomad4 AMR

AF:

0.0343

Gnomad4 ASJ

AF:

0.0418

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.0315

Gnomad4 FIN

AF:

0.0768

Gnomad4 NFE

AF:

0.0787

Gnomad4 OTH

AF:

0.0416

Alfa

AF:

0.0683

Hom.:

636

Bravo

AF:

0.0459

TwinsUK

AF:

0.0777

AC:

288

ALSPAC

AF:

0.0859

AC:

331

ESP6500AA

AF:

0.0135

AC:

ESP6500EA

AF:

0.0731

AC:

602

ExAC

AF:

0.0522

AC:

6311

Asia WGS

AF:

0.0190

AC:

AN:

3478

EpiCase

AF:

0.0710

EpiControl

AF:

0.0690

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 11, 2019	This variant is associated with the following publications: (PMID: 28379579) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.14

.;T

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.31

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.84

T;D

MetaRNN

Benign

0.0025

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.1

.;L

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-3.5

D;D

REVEL

Uncertain

0.29

Sift

Benign

0.053

T;T

Sift4G

Uncertain

0.035

D;D

Polyphen

0.030

B;B

Vest4

0.070

MPC

0.28

ClinPred

0.025

GERP RS

4.0

Varity_R

0.14

gMVP

0.40

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