1-45488361-G-A

Variant names:

• chr1-45488361-G-A
• rs12743512
• NM_007170.3:c.-87+2491C>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.-87+2491C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 151,934 control chromosomes in the GnomAD database, including 13,094 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 0.40 (13094 hom., cov: 32)
• Consequence: TESK2 NM_007170.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.217
• Publications: 16 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.558 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TESK2	NM_007170.3	MANE Select	c.-87+2491C>T		intron	N/A	NP_009101.2
	TESK2	NM_001320800.2		c.-28+2491C>T		intron	N/A	NP_001307729.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TESK2	ENST00000372086.4	TSL:1 MANE Select	c.-87+2491C>T		intron	N/A	ENSP00000361158.3
	ENSG00000288208	ENST00000671898.1		n.-87+2491C>T		intron	N/A	ENSP00000499896.1
	TESK2	ENST00000486676.5	TSL:5	n.310+2491C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61363 AN: 151816 Hom.: 13101 Cov.: 32

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.414

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

GnomAD4 genome AF: 0.404 AC: 61352 AN: 151934 Hom.: 13094 Cov.: 32 AF XY: 0.411 AC XY: 30480 AN XY: 74248

African (AFR) AF: 0.260 AC: 10772 AN: 41440

American (AMR) AF: 0.469 AC: 7147 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 1644 AN: 3466

East Asian (EAS) AF: 0.575 AC: 2977 AN: 5174

South Asian (SAS) AF: 0.502 AC: 2418 AN: 4814

European-Finnish (FIN) AF: 0.480 AC: 5055 AN: 10530

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.440 AC: 29914 AN: 67952

Other (OTH) AF: 0.409 AC: 862 AN: 2108

Alfa AF: 0.409 Hom.: 10860

Bravo AF: 0.395

Asia WGS AF: 0.503 AC: 1746 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	9.2
DANN	Benign	0.74
PhyloP100		0.22
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: rs12743512; hg19: chr1-45954033;