NM_007170.3:c.996G>C

Variant names:

• chr1-45345878-C-G
• rs778883567
• NM_007170.3:c.996G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007170.3(TESK2):​c.996G>C​(p.Arg332Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 19/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R332T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: TESK2 NM_007170.3 missense, splice_region
• Scores: Splicing: ADA: 0.0002672
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0330
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08557603).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TESK2	NM_007170.3	MANE Select	c.996G>C	p.Arg332Ser	missense splice_region	Exon 10 of 11	NP_009101.2	Q96S53-1
	TESK2	NM_001320800.2		c.747G>C	p.Arg249Ser	missense splice_region	Exon 9 of 10	NP_001307729.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TESK2	ENST00000372086.4	TSL:1 MANE Select	c.996G>C	p.Arg332Ser	missense splice_region	Exon 10 of 11	ENSP00000361158.3	Q96S53-1
	TESK2	ENST00000372084.5	TSL:1	c.909G>C	p.Arg303Ser	missense splice_region	Exon 8 of 9	ENSP00000361156.1	Q96S53-3
	ENSG00000288208	ENST00000671898.1		n.540+9425G>C		intron	N/A	ENSP00000499896.1	A0A5F9ZGZ0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 249470 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461076 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726900

African (AFR) AF: 0.0000299 AC: 1 AN: 33458

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5628

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111462

Other (OTH) AF: 0.0000331 AC: 2 AN: 60346

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	7.7
DANN	Benign	0.96
DEOGEN2	Benign	0.0083	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.69	N
PhyloP100		0.033
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.060	N
REVEL	Benign	0.045
Sift	Benign	0.098	T
Sift4G	Benign	0.45	T
Polyphen		0.0	B
Vest4		0.16
MutPred		0.29		Loss of MoRF binding (P = 0.0103)
MVP		0.60
MPC		0.22
ClinPred		0.074	T
GERP RS		0.57
Varity_R		0.088
gMVP		0.36
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00027
dbscSNV1_RF	Benign	0.026
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: rs778883567; hg19: chr1-45811550;