chr1-45345878-C-G

Position:

chr1-45345878-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007170.3(TESK2):c.996G>C(p.Arg332Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R332T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

TESK2
NM_007170.3 missense, splice_region

Scores

Splicing: ADA: 0.0002672

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0330

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08557603).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TESK2	NM_007170.3 link	c.996G>C	p.Arg332Ser	missense_variant, splice_region_variant	10/11	ENST00000372086.4	NP_009101.2	Q96S53-1
TESK2	NM_001320800.2 link	c.747G>C	p.Arg249Ser	missense_variant, splice_region_variant	9/10		NP_001307729.1	Q96S53B4DFN2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TESK2	ENST00000372086.4 link	c.996G>C	p.Arg332Ser	missense_variant, splice_region_variant	10/11	1	NM_007170.3	ENSP00000361158.3	Q96S53-1
TESK2	ENST00000372084.5 link	c.909G>C	p.Arg303Ser	missense_variant, splice_region_variant	8/9	1		ENSP00000361156.1	Q96S53-3
ENSG00000288208	ENST00000671898.1 link	n.540+9425G>C		intron_variant				ENSP00000499896.1	A0A5F9ZGZ0
TESK2	ENST00000486676.5 link	n.1343G>C		splice_region_variant, non_coding_transcript_exon_variant	9/10	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

249470

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135336

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461076

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726900

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

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

Aug 28, 2023

The c.996G>C (p.R332S) alteration is located in exon 10 (coding exon 9) of the TESK2 gene. This alteration results from a G to C substitution at nucleotide position 996, causing the arginine (R) at amino acid position 332 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

0.13

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.56

CADD

Benign

7.7

DANN

Benign

0.96

DEOGEN2

Benign

0.0083

.;T

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.63

T;T

M_CAP

Benign

0.031

MetaRNN

Benign

0.086

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.69

.;N

PrimateAI

Benign

0.30

PROVEAN

Benign

0.060

N;N

REVEL

Benign

0.045

Sift

Benign

0.098

T;T

Sift4G

Benign

0.45

T;T

Polyphen

0.0

B;B

Vest4

0.16

MutPred

0.29

.;Loss of MoRF binding (P = 0.0103);

MVP

0.60

MPC

0.22

ClinPred

0.074

GERP RS

0.57

Varity_R

0.088

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00027

dbscSNV1_RF

Benign

0.026

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