chr9-35608892-C-T

Variant summary

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

The NM_006285.3(TESK1):​c.1031C>T​(p.Thr344Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000206 in 1,600,426 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 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

TESK1
NM_006285.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.36
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]

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=0.24372691).
BS2
High AC in GnomAdExome4 at 29 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TESK1NM_006285.3 linkc.1031C>T p.Thr344Met missense_variant Exon 10 of 10 ENST00000336395.6 NP_006276.2 Q15569Q8NFJ4
TESK1NM_001318230.2 linkc.551C>T p.Thr184Met missense_variant Exon 9 of 9 NP_001305159.1 Q15569

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TESK1ENST00000336395.6 linkc.1031C>T p.Thr344Met missense_variant Exon 10 of 10 1 NM_006285.3 ENSP00000338127.5 Q15569
TESK1ENST00000498522.5 linkn.1077C>T non_coding_transcript_exon_variant Exon 9 of 9 1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152154
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
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:
0.0000942
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000371
AC:
9
AN:
242428
Hom.:
0
AF XY:
0.0000382
AC XY:
5
AN XY:
130902
show subpopulations
Gnomad AFR exome
AF:
0.0000621
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:
0.0000477
Gnomad NFE exome
AF:
0.0000638
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000200
AC:
29
AN:
1448272
Hom.:
0
Cov.:
31
AF XY:
0.0000167
AC XY:
12
AN XY:
719046
show subpopulations
Gnomad4 AFR exome
AF:
0.0000604
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:
0.0000756
Gnomad4 NFE exome
AF:
0.0000172
Gnomad4 OTH exome
AF:
0.0000503
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152154
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74320
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000942
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000302
ExAC
AF:
0.0000577
AC:
7

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 31, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1031C>T (p.T344M) alteration is located in exon 10 (coding exon 10) of the TESK1 gene. This alteration results from a C to T substitution at nucleotide position 1031, causing the threonine (T) at amino acid position 344 to be replaced by a methionine (M). 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
0.090
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.26
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.041
T;T
Eigen
Benign
0.012
Eigen_PC
Benign
0.055
FATHMM_MKL
Benign
0.58
D
LIST_S2
Benign
0.77
T;.
M_CAP
Benign
0.027
D
MetaRNN
Benign
0.24
T;T
MetaSVM
Benign
-0.72
T
MutationAssessor
Benign
0.69
N;N
PrimateAI
Uncertain
0.55
T
PROVEAN
Benign
-0.69
.;N
REVEL
Benign
0.17
Sift
Benign
0.070
.;T
Sift4G
Benign
0.11
T;T
Polyphen
0.99
D;D
Vest4
0.45
MutPred
0.11
Loss of phosphorylation at T344 (P = 0.024);Loss of phosphorylation at T344 (P = 0.024);
MVP
0.46
MPC
0.34
ClinPred
0.057
T
GERP RS
5.3
Varity_R
0.046
gMVP
0.28

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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.

Other links and lift over

dbSNP: rs754529433; hg19: chr9-35608889; COSMIC: COSV52411907; COSMIC: COSV52411907; API