Variant 19-19514994-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032037.4(TSSK6):c.434C>G(p.Pro145Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,609,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

TSSK6
NM_032037.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.51

Variant links:

Genes affected

TSSK6 (HGNC:30410): (testis specific serine kinase 6) This intronless gene encodes a member of the CAMK (calcium/calmodulin-dependent) serine/threonine protein kinase family. The encoded kinase has a broad expression pattern but is described as testis-specific due to effects on fertility. Male mice which lack the gene encoding a highly similar protein are sterile and have morphologically abnormal sperm. [provided by RefSeq, Jan 2012]

TSSK6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09375498).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSSK6	NM_032037.4 linkuse as main transcript	c.434C>G	p.Pro145Arg	missense_variant	1/1	ENST00000585580.4	NP_114426.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSSK6	ENST00000585580.4 linkuse as main transcript	c.434C>G	p.Pro145Arg	missense_variant	1/1		NM_032037.4	ENSP00000466477	P1
TSSK6	ENST00000587522.3 linkuse as main transcript	c.434C>G	p.Pro145Arg	missense_variant, NMD_transcript_variant	1/2	2		ENSP00000466056

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000404

AC:

AN:

247302

Hom.:

AF XY:

0.00000746

AC XY:

AN XY:

134124

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000897

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000240

AC:

AN:

1457592

Hom.:

Cov.:

AF XY:

0.0000235

AC XY:

AN XY:

724810

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000288

Gnomad4 OTH exome

AF:

0.0000498

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000903

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 24, 2022

The c.434C>G (p.P145R) alteration is located in exon 1 (coding exon 1) of the TSSK6 gene. This alteration results from a C to G substitution at nucleotide position 434, causing the proline (P) at amino acid position 145 to be replaced by an arginine (R). 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

Benign

0.12

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.048

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.35

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.62

M_CAP

Benign

0.0063

MetaRNN

Benign

0.094

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.27

MutationTaster

Benign

0.97

N;N

PrimateAI

Uncertain

0.66

Sift4G

Benign

0.51

Polyphen

0.0040

Vest4

0.25

MVP

0.17

ClinPred

0.032

GERP RS

2.5

Varity_R

0.048

gMVP

0.68

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over