1-45384918-A-G

Variant names:

• chr1-45384918-A-G
• rs1417578
• NM_007170.3:c.393+994T>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.393+994T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 151,806 control chromosomes in the GnomAD database, including 11,883 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 (11883 hom., cov: 30)
• Consequence: TESK2 NM_007170.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.632
• Publications: 1 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TESK2	NM_007170.3	c.393+994T>C		intron_variant	Intron 4 of 10	ENST00000372086.4	NP_009101.2
TESK2	NM_001320800.2	c.144+994T>C		intron_variant	Intron 3 of 9		NP_001307729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TESK2	ENST00000372086.4	c.393+994T>C		intron_variant	Intron 4 of 10	1	NM_007170.3	ENSP00000361158.3
TESK2	ENST00000372084.5	c.393+994T>C		intron_variant	Intron 3 of 8	1		ENSP00000361156.1
ENSG00000288208	ENST00000671898.1	n.393+994T>C		intron_variant	Intron 4 of 20			ENSP00000499896.1
TESK2	ENST00000486676.5	n.741-29469T>C		intron_variant	Intron 3 of 9	5

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54943 AN: 151690 Hom.: 11825 Cov.: 30

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.355

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

GnomAD4 genome AF: 0.363 AC: 55065 AN: 151806 Hom.: 11883 Cov.: 30 AF XY: 0.360 AC XY: 26724 AN XY: 74206

African (AFR) AF: 0.590 AC: 24407 AN: 41356

American (AMR) AF: 0.439 AC: 6684 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 888 AN: 3464

East Asian (EAS) AF: 0.397 AC: 2049 AN: 5162

South Asian (SAS) AF: 0.237 AC: 1139 AN: 4806

European-Finnish (FIN) AF: 0.212 AC: 2234 AN: 10536

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16554 AN: 67928

Other (OTH) AF: 0.362 AC: 764 AN: 2112

Alfa AF: 0.304 Hom.: 1098

Bravo AF: 0.392

Asia WGS AF: 0.377 AC: 1312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.8
DANN	Benign	0.75
PhyloP100		0.63
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1417578; hg19: chr1-45850590;