rs200035854

Variant names:

• chr1-45345243-A-G
• rs200035854
• NM_007170.3:c.1313T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_007170.3(TESK2):​c.1313T>C​(p.Met438Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000917 in 1,614,218 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000070 (1 hom.)
• Consequence: TESK2 NM_007170.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.195
• Publications: 0 publications found

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]

ENSG00000288208 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005867064).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007170.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TESK2	NM_007170.3	MANE Select	c.1313T>C	p.Met438Thr	missense	Exon 11 of 11	NP_009101.2	Q96S53-1
	TESK2	NM_001320800.2		c.1064T>C	p.Met355Thr	missense	Exon 10 of 10	NP_001307729.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TESK2	ENST00000372086.4	TSL:1 MANE Select	c.1313T>C	p.Met438Thr	missense	Exon 11 of 11	ENSP00000361158.3	Q96S53-1
	TESK2	ENST00000372084.5	TSL:1	c.1226T>C	p.Met409Thr	missense	Exon 9 of 9	ENSP00000361156.1	Q96S53-3
	ENSG00000288208	ENST00000671898.1		n.540+10060T>C		intron	N/A	ENSP00000499896.1	A0A5F9ZGZ0

Frequencies

GnomAD3 genomes AF: 0.000302 AC: 46 AN: 152216 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

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: 0.000478

GnomAD2 exomes AF: 0.000269 AC: 67 AN: 249352 AF XY: 0.000236

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00188

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000330

GnomAD4 exome AF: 0.0000698 AC: 102 AN: 1461884 Hom.: 1 Cov.: 31 AF XY: 0.0000523 AC XY: 38 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00215 AC: 96 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112012

Other (OTH) AF: 0.0000828 AC: 5 AN: 60396

GnomAD4 genome AF: 0.000302 AC: 46 AN: 152334 Hom.: 0 Cov.: 32 AF XY: 0.000416 AC XY: 31 AN XY: 74480

African (AFR) AF: 0.0000241 AC: 1 AN: 41564

American (AMR) AF: 0.00287 AC: 44 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.0000522 Hom.: 0

Bravo AF: 0.000317

ExAC AF: 0.000149 AC: 18

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	2.1
DANN	Benign	0.67
DEOGEN2	Benign	0.0043	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.0059	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.2	N
PhyloP100		0.20
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.57	N
REVEL	Benign	0.079
Sift	Benign	0.47	T
Sift4G	Benign	0.64	T
Polyphen		0.0	B
Vest4		0.030
MVP		0.43
MPC		0.23
ClinPred		0.021	T
GERP RS		2.0
Varity_R		0.049
gMVP		0.16
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs200035854; hg19: chr1-45810915;