Variant 19-19514749-C-T 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.679G>A(p.Gly227Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000493 in 1,602,316 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000053 ( 0 hom. )

Consequence

TSSK6
NM_032037.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.88

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=0.09098178).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSSK6	NM_032037.4 linkuse as main transcript	c.679G>A	p.Gly227Ser	missense_variant	1/1	ENST00000585580.4	NP_114426.1	Q9BXA6A0A024R7Q5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TSSK6	ENST00000585580.4 linkuse as main transcript	c.679G>A	p.Gly227Ser	missense_variant	1/1	6	NM_032037.4	ENSP00000466477.1	Q9BXA6
TSSK6	ENST00000587522.3 linkuse as main transcript	n.679G>A		non_coding_transcript_exon_variant	1/2	2		ENSP00000466056.1	Q9BXA6
TSSK6	ENST00000602623.1 linkuse as main transcript	n.187G>A		non_coding_transcript_exon_variant	1/2	3		ENSP00000473413.1	R4GMZ2

Frequencies

GnomAD3 genomes

AF:

0.0000131

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:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000105

AC:

AN:

237826

Hom.:

AF XY:

0.000146

AC XY:

AN XY:

130414

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:

0.000819

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000531

AC:

AN:

1450084

Hom.:

Cov.:

AF XY:

0.0000790

AC XY:

AN XY:

721876

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:

0.000870

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74370

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:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.000149

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

Mar 01, 2023

The c.679G>A (p.G227S) alteration is located in exon 1 (coding exon 1) of the TSSK6 gene. This alteration results from a G to A substitution at nucleotide position 679, causing the glycine (G) at amino acid position 227 to be replaced by a serine (S). 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

0.45

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.82

M_CAP

Benign

0.045

MetaRNN

Benign

0.091

MetaSVM

Benign

-0.67

MutationAssessor

Benign

1.3

PrimateAI

Pathogenic

0.84

Sift4G

Benign

0.68

Polyphen

0.78

Vest4

0.41

MutPred

0.42

Gain of phosphorylation at G227 (P = 0.0477);

MVP

0.54

ClinPred

0.33

GERP RS

5.0

Varity_R

0.14

gMVP

0.69

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