1-45384918-A-G

Position:

• chr1-45384918-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.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

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=-0.84).
• 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/exons	MANE	Protein	UniProt
TESK2	NM_007170.3	c.393+994T>C		intron_variant		ENST00000372086.4	NP_009101.2
TESK2	NM_001320800.2	c.144+994T>C		intron_variant			NP_001307729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TESK2	ENST00000372086.4	c.393+994T>C		intron_variant		1	NM_007170.3	ENSP00000361158	P1
TESK2	ENST00000372084.5	c.393+994T>C		intron_variant		1		ENSP00000361156
TESK2	ENST00000486676.5	n.741-29469T>C		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.590

Gnomad4 AMR AF: 0.439

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.397

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.212

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.362

Alfa AF: 0.291 Hom.: 957

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1417578; hg19: chr1-45850590;