chr1-45353397-C-T

Position:

• chr1-45353397-C-T

Variant summary

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

The NM_007170.3(TESK2):​c.540+1906G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,114 control chromosomes in the GnomAD database, including 5,771 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 0.27 (5771 hom., cov: 32)
• Consequence: TESK2 NM_007170.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.28

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TESK2	NM_007170.3	c.540+1906G>A		intron_variant		ENST00000372086.4	NP_009101.2
TESK2	NM_001320800.2	c.291+1906G>A		intron_variant			NP_001307729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TESK2	ENST00000372086.4	c.540+1906G>A		intron_variant		1	NM_007170.3	ENSP00000361158.3
TESK2	ENST00000372084.5	c.540+1906G>A		intron_variant		1		ENSP00000361156.1
ENSG00000288208	ENST00000671898.1	n.540+1906G>A		intron_variant				ENSP00000499896.1
TESK2	ENST00000486676.5	n.887+1906G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40737 AN: 151996 Hom.: 5748 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.268 AC: 40785 AN: 152114 Hom.: 5771 Cov.: 32 AF XY: 0.267 AC XY: 19882 AN XY: 74380

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.404

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.365

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.208

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.302

Alfa AF: 0.253 Hom.: 905

Bravo AF: 0.285

Asia WGS AF: 0.337 AC: 1172 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	1.4
DANN	Benign	0.19

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: rs7544178; hg19: chr1-45819069;