Variant 9-35608973-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000336395.6(TESK1):c.1112G>C(p.Trp371Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000179 in 1,613,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

TESK1
ENST00000336395.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.80

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:

TESK1 (HGNC:):

TESK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09863055).

BS2

High AC in GnomAd4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TESK1	NM_006285.3 linkuse as main transcript	c.1112G>C	p.Trp371Ser	missense_variant	10/10	ENST00000336395.6	NP_006276.2	Q15569Q8NFJ4
TESK1	NM_001318230.2 linkuse as main transcript	c.632G>C	p.Trp211Ser	missense_variant	9/9		NP_001305159.1	Q15569

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TESK1	ENST00000336395.6 linkuse as main transcript	c.1112G>C	p.Trp371Ser	missense_variant	10/10	1	NM_006285.3	ENSP00000338127.5		Q15569
TESK1	ENST00000498522.5 linkuse as main transcript	n.1158G>C		non_coding_transcript_exon_variant	9/9	1

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000995

AC:

AN:

251310

Hom.:

AF XY:

0.000125

AC XY:

AN XY:

135824

show subpopulations

Gnomad AFR exome

AF:

0.0000615

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:

0.000185

Gnomad NFE exome

AF:

0.000167

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000191

AC:

279

AN:

1461802

Hom.:

Cov.:

AF XY:

0.000194

AC XY:

141

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000169

Gnomad4 NFE exome

AF:

0.000240

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000171

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.0000988

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000237

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

Jun 28, 2022

The c.1112G>C (p.W371S) alteration is located in exon 10 (coding exon 10) of the TESK1 gene. This alteration results from a G to C substitution at nucleotide position 1112, causing the tryptophan (W) at amino acid position 371 to be replaced by a serine (S). 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

0.089

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.027

T;T

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.23

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.61

T;.

M_CAP

Benign

0.024

MetaRNN

Benign

0.099

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;L

MutationTaster

Benign

1.0

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.96

.;N

REVEL

Benign

0.22

Sift

Benign

0.25

.;T

Sift4G

Benign

0.41

T;T

Polyphen

0.22

B;B

Vest4

0.28

MVP

0.54

MPC

0.30

ClinPred

0.066

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.15

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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