rs9429072

chr1-45344419-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007170.3(TESK2):c.*421T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 176,444 control chromosomes in the GnomAD database, including 12,297 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.36 (11372 hom., cov: 32)
  • Exomes 𝑓: 0.24 (925 hom.)
• Consequence: TESK2 NM_007170.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0360

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TESK2	NM_007170.3	c.*421T>C		3_prime_UTR_variant	11/11	ENST00000372086.4
TESK2	NM_001320800.2	c.*421T>C		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TESK2	ENST00000372086.4	c.*421T>C		3_prime_UTR_variant	11/11	1	NM_007170.3	P1
TESK2	ENST00000372084.5	c.*421T>C		3_prime_UTR_variant	9/9	1
TESK2	ENST00000486676.5	n.2484T>C		non_coding_transcript_exon_variant	10/10	5

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54181 AN: 152022 Hom.: 11320 Cov.: 32

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.350

GnomAD4 exome AF: 0.243 AC: 5915 AN: 24302 Hom.: 925 Cov.: 0 AF XY: 0.241 AC XY: 2992 AN XY: 12440

Gnomad4 AFR exome AF: 0.535

Gnomad4 AMR exome AF: 0.420

Gnomad4 ASJ exome AF: 0.212

Gnomad4 EAS exome AF: 0.346

Gnomad4 SAS exome AF: 0.194

Gnomad4 FIN exome AF: 0.213

Gnomad4 NFE exome AF: 0.209

Gnomad4 OTH exome AF: 0.252

GnomAD4 genome AF: 0.357 AC: 54294 AN: 152142 Hom.: 11372 Cov.: 32 AF XY: 0.355 AC XY: 26390 AN XY: 74396

Gnomad4 AFR AF: 0.567

Gnomad4 AMR AF: 0.439

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.397

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.358

Alfa AF: 0.285 Hom.: 6977

Bravo AF: 0.386

Asia WGS AF: 0.376 AC: 1307 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.34
Dann	Benign	0.42

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

Other links and lift over

dbSNP: rs9429072; hg19: chr1-45810091; COSMIC: COSV59155666; COSMIC: COSV59155666;