rs781062

Variant names:

• chr1-45467066-T-A
• rs781062
• NM_007170.3:c.-86-9195A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007170.3(TESK2):​c.-86-9195A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 151,870 control chromosomes in the GnomAD database, including 3,450 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 0.20 (3450 hom., cov: 31)
• Consequence: TESK2 NM_007170.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.468
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TESK2	NM_007170.3	c.-86-9195A>T		intron_variant	Intron 1 of 10	ENST00000372086.4	NP_009101.2
TESK2	NM_001320800.2	c.-28+23786A>T		intron_variant	Intron 1 of 9		NP_001307729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TESK2	ENST00000372086.4	c.-86-9195A>T		intron_variant	Intron 1 of 10	1	NM_007170.3	ENSP00000361158.3
ENSG00000288208	ENST00000671898.1	n.-86-9195A>T		intron_variant	Intron 1 of 20			ENSP00000499896.1
TESK2	ENST00000486676.5	n.311-9195A>T		intron_variant	Intron 1 of 9	5

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30848 AN: 151752 Hom.: 3444 Cov.: 31

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.0380

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.213

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.203 AC: 30876 AN: 151870 Hom.: 3450 Cov.: 31 AF XY: 0.197 AC XY: 14637 AN XY: 74220

African (AFR) AF: 0.140 AC: 5812 AN: 41430

American (AMR) AF: 0.163 AC: 2484 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 875 AN: 3466

East Asian (EAS) AF: 0.0384 AC: 199 AN: 5176

South Asian (SAS) AF: 0.210 AC: 1013 AN: 4820

European-Finnish (FIN) AF: 0.186 AC: 1960 AN: 10526

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.263 AC: 17848 AN: 67922

Other (OTH) AF: 0.211 AC: 444 AN: 2104

Alfa AF: 0.241 Hom.: 560

Bravo AF: 0.198

Asia WGS AF: 0.122 AC: 426 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.9
DANN	Benign	0.35
PhyloP100		0.47
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: rs781062; hg19: chr1-45932738;