5-113434143-C-T

Position:

chr5-113434143-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032028.4(TSSK1B):c.697G>A(p.Val233Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000397 in 1,614,026 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. 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. V233L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

TSSK1B
NM_032028.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.495

Variant links:

Genes affected

TSSK1B (HGNC:14968): (testis specific serine kinase 1B) TSSK1 belongs to a family of serine/threonine kinases highly expressed in testis (Hao et al., 2004 [PubMed 15044604]).[supplied by OMIM, Mar 2008]

TSSK1B links:

MCC (HGNC:6935): (MCC regulator of WNT signaling pathway) This gene is a candidate colorectal tumor suppressor gene that is thought to negatively regulate cell cycle progression. The orthologous gene in the mouse expresses a phosphoprotein associated with the plasma membrane and membrane organelles, and overexpression of the mouse protein inhibits entry into S phase. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

MCC links:

ENSG00000232633 (HGNC:):

ENSG00000232633 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.044219106).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSSK1B	NM_032028.4 linkuse as main transcript	c.697G>A	p.Val233Ile	missense_variant	1/1	ENST00000390666.4	NP_114417.1	Q9BXA7A0ZT98
MCC	NM_001085377.2 linkuse as main transcript	c.171-48931G>A		intron_variant		ENST00000408903.7	NP_001078846.2	P23508-2
LOC107986366	XR_001742459.2 linkuse as main transcript	n.179+5364C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TSSK1B	ENST00000390666.4 linkuse as main transcript	c.697G>A	p.Val233Ile	missense_variant	1/1	6	NM_032028.4	ENSP00000375081.3	Q9BXA7
MCC	ENST00000408903.7 linkuse as main transcript	c.171-48931G>A		intron_variant		2	NM_001085377.2	ENSP00000386227.3	P23508-2
ENSG00000232633	ENST00000416046.2 linkuse as main transcript	n.1540C>T		non_coding_transcript_exon_variant	4/5	2

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000636

AC:

AN:

251388

Hom.:

AF XY:

0.0000515

AC XY:

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000703

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000376

AC:

AN:

1461872

Hom.:

Cov.:

AF XY:

0.0000385

AC XY:

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000220

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000279

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000592

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000642

ExAC

AF:

0.0000741

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

Dec 09, 2023

The c.697G>A (p.V233I) alteration is located in exon 1 (coding exon 1) of the TSSK1B gene. This alteration results from a G to A substitution at nucleotide position 697, causing the valine (V) at amino acid position 233 to be replaced by an isoleucine (I). 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

0.084

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.66

CADD

Benign

8.8

DANN

Benign

0.94

DEOGEN2

Benign

0.071

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0025

LIST_S2

Benign

0.76

M_CAP

Benign

0.0040

MetaRNN

Benign

0.044

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.23

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.38

REVEL

Benign

0.046

Sift

Benign

0.20

Sift4G

Benign

0.12

Polyphen

0.024

Vest4

0.037

MutPred

0.36

Loss of MoRF binding (P = 0.1131);

MVP

0.32

MPC

0.087

ClinPred

0.016

GERP RS

-0.54

Varity_R

0.055

gMVP

0.12

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