Genetic Variant TESK1:p.Arg164Trp (chr9-35606936-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_006285.3(TESK1):c.490C>T(p.Arg164Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000285 in 1,612,822 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

TESK1
NM_006285.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.828

Variant links:

Genes affected

TESK1 (HGNC:11731): (testis associated actin remodelling kinase 1) This gene product is a serine/threonine protein kinase that contains an N-terminal protein kinase domain and a C-terminal proline-rich domain. Its protein kinase domain is most closely related to those of the LIM motif-containing protein kinases (LIMKs). The encoded protein can phosphorylate myelin basic protein and histone in vitro. The testicular germ cell-specific expression and developmental pattern of expression of the mouse gene suggests that this gene plays an important role at and after the meiotic phase of spermatogenesis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

TESK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TESK1	NM_006285.3 link	c.490C>T	p.Arg164Trp	missense_variant	Exon 4 of 10	ENST00000336395.6	NP_006276.2	Q15569Q8NFJ4
TESK1	NM_001318230.2 link	c.93C>T	p.Cys31Cys	synonymous_variant	Exon 4 of 9		NP_001305159.1	Q15569

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TESK1	ENST00000336395.6 link	c.490C>T	p.Arg164Trp	missense_variant	Exon 4 of 10	1	NM_006285.3	ENSP00000338127.5	Q15569
TESK1	ENST00000498522.5 link	n.619C>T		non_coding_transcript_exon_variant	Exon 4 of 9	1
TESK1	ENST00000467424.5 link	n.-36C>T		upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000360

AC:

AN:

249658

Hom.:

AF XY:

0.00000741

AC XY:

AN XY:

135022

show subpopulations

Gnomad AFR exome

AF:

0.000433

Gnomad AMR exome

AF:

0.00

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:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000205

AC:

AN:

1460644

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

726622

show subpopulations

Gnomad4 AFR exome

AF:

0.000389

Gnomad4 AMR exome

AF:

0.00

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:

0.0000144

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000105

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.000338

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.000132

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000577

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.490C>T (p.R164W) alteration is located in exon 4 (coding exon 4) of the TESK1 gene. This alteration results from a C to T substitution at nucleotide position 490, causing the arginine (R) at amino acid position 164 to be replaced by a tryptophan (W). 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

0.18

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.19

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.66

D;D

Eigen

Uncertain

0.27

Eigen_PC

Benign

0.22

FATHMM_MKL

Benign

0.74

LIST_S2

Pathogenic

0.98

D;.

M_CAP

Benign

0.078

MetaRNN

Uncertain

0.57

D;D

MetaSVM

Benign

-0.31

MutationAssessor

Benign

1.9

L;L

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-3.8

.;D

REVEL

Uncertain

0.37

Sift

Uncertain

0.0050

.;D

Sift4G

Uncertain

0.015

D;D

Polyphen

1.0

D;D

Vest4

0.53

MVP

0.70

MPC

2.3

ClinPred

0.49

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.23

gMVP

0.77

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