rs9429072

Variant names:

• chr1-45344419-A-G
• rs9429072
• NM_007170.3:c.*421T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 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: Benign. The variant received -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.

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.*421T>C		3_prime_UTR	Exon 11 of 11	NP_009101.2	Q96S53-1
	TESK2	NM_001320800.2		c.*421T>C		3_prime_UTR	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.*421T>C		3_prime_UTR	Exon 11 of 11	ENSP00000361158.3	Q96S53-1
	TESK2	ENST00000372084.5	TSL:1	c.*421T>C		3_prime_UTR	Exon 9 of 9	ENSP00000361156.1	Q96S53-3
	ENSG00000288208	ENST00000671898.1		n.541-9908T>C		intron	N/A	ENSP00000499896.1	A0A5F9ZGZ0

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

African (AFR) AF: 0.535 AC: 199 AN: 372

American (AMR) AF: 0.420 AC: 1057 AN: 2516

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 98 AN: 462

East Asian (EAS) AF: 0.346 AC: 357 AN: 1032

South Asian (SAS) AF: 0.194 AC: 430 AN: 2220

European-Finnish (FIN) AF: 0.213 AC: 262 AN: 1232

Middle Eastern (MID) AF: 0.371 AC: 26 AN: 70

European-Non Finnish (NFE) AF: 0.209 AC: 3154 AN: 15078

Other (OTH) AF: 0.252 AC: 332 AN: 1320

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

African (AFR) AF: 0.567 AC: 23508 AN: 41480

American (AMR) AF: 0.439 AC: 6697 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 889 AN: 3468

East Asian (EAS) AF: 0.397 AC: 2055 AN: 5178

South Asian (SAS) AF: 0.240 AC: 1159 AN: 4830

European-Finnish (FIN) AF: 0.214 AC: 2272 AN: 10598

Middle Eastern (MID) AF: 0.325 AC: 95 AN: 292

European-Non Finnish (NFE) AF: 0.244 AC: 16614 AN: 67998

Other (OTH) AF: 0.358 AC: 756 AN: 2114

Alfa AF: 0.298 Hom.: 11225

Bravo AF: 0.386

Asia WGS AF: 0.376 AC: 1307 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.34
DANN	Benign	0.42
PhyloP100		-0.036
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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