9-35608443-G-A

Position:

• chr9-35608443-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000336395.6(TESK1):​c.934G>A​(p.Glu312Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TESK1 ENST00000336395.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.68

Genes affected

TESK1 (HGNC:11731): (testis associated actin remodelling kinase 1) This gene product is a serine/threonine protein kinase that contains an N-terminal protein kinase domain and a C-terminal proline-rich domain. Its protein kinase domain is most closely related to those of the LIM motif-containing protein kinases (LIMKs). The encoded protein can phosphorylate myelin basic protein and histone in vitro. The testicular germ cell-specific expression and developmental pattern of expression of the mouse gene suggests that this gene plays an important role at and after the meiotic phase of spermatogenesis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

TESK1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TESK1	NM_006285.3	c.934G>A	p.Glu312Lys	missense_variant	9/10	ENST00000336395.6	NP_006276.2
TESK1	NM_001318230.2	c.454G>A	p.Glu152Lys	missense_variant	8/9		NP_001305159.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TESK1	ENST00000336395.6	c.934G>A	p.Glu312Lys	missense_variant	9/10	1	NM_006285.3	ENSP00000338127.5
TESK1	ENST00000498522.5	n.980G>A		non_coding_transcript_exon_variant	8/9	1
TESK1	ENST00000480077.2	n.*8G>A		downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 05, 2024

The c.934G>A (p.E312K) alteration is located in exon 9 (coding exon 9) of the TESK1 gene. This alteration results from a G to A substitution at nucleotide position 934, causing the glutamic acid (E) at amino acid position 312 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.54	D;D
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.80	T;.
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.63	D;D
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.5	L;L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-2.8	.;D
REVEL	Benign	0.21
Sift	Benign	0.11	.;T
Sift4G	Benign	0.12	T;T
Polyphen		0.61	P;P
Vest4		0.73
MutPred		0.65		Gain of methylation at E312 (P = 0.012);Gain of methylation at E312 (P = 0.012);
MVP		0.21
MPC		0.77
ClinPred		0.98	D
GERP RS		5.3
Varity_R		0.25
gMVP		0.80

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-35608440;