chr5-113433855-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.985G>A​(p.Glu329Lys) 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 1,614,012 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 (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

TSSK1B
NM_032028.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.189
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]
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]

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=0.05623409).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TSSK1BNM_032028.4 linkc.985G>A p.Glu329Lys missense_variant Exon 1 of 1 ENST00000390666.4 NP_114417.1 Q9BXA7A0ZT98
MCCNM_001085377.2 linkc.171-48643G>A intron_variant Intron 1 of 18 ENST00000408903.7 NP_001078846.2 P23508-2
LOC107986366XR_001742459.2 linkn.179+5076C>T intron_variant Intron 2 of 4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TSSK1BENST00000390666.4 linkc.985G>A p.Glu329Lys missense_variant Exon 1 of 1 6 NM_032028.4 ENSP00000375081.3 Q9BXA7
MCCENST00000408903.7 linkc.171-48643G>A intron_variant Intron 1 of 18 2 NM_001085377.2 ENSP00000386227.3 P23508-2
ENSG00000232633ENST00000416046.2 linkn.1252C>T non_coding_transcript_exon_variant Exon 4 of 5 2

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152226
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000145
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000385
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000161
AC:
4
AN:
249068
Hom.:
0
AF XY:
0.0000222
AC XY:
3
AN XY:
135130
show subpopulations
Gnomad AFR exome
AF:
0.000129
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000376
AC:
55
AN:
1461668
Hom.:
0
Cov.:
31
AF XY:
0.0000385
AC XY:
28
AN XY:
727104
show subpopulations
Gnomad4 AFR exome
AF:
0.000179
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000387
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000591
AC:
9
AN:
152344
Hom.:
0
Cov.:
33
AF XY:
0.0000805
AC XY:
6
AN XY:
74488
show subpopulations
Gnomad4 AFR
AF:
0.000168
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000322
Hom.:
0
Bravo
AF:
0.0000680
ESP6500AA
AF:
0.000251
AC:
1
ESP6500EA
AF:
0.000120
AC:
1
ExAC
AF:
0.0000248
AC:
3

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 16, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.985G>A (p.E329K) 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 985, causing the glutamic acid (E) at amino acid position 329 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
Benign
0.068
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
2.5
DANN
Benign
0.82
DEOGEN2
Benign
0.043
T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.00065
N
LIST_S2
Benign
0.50
T
M_CAP
Benign
0.0056
T
MetaRNN
Benign
0.056
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.4
L
PrimateAI
Benign
0.30
T
PROVEAN
Benign
-0.69
N
REVEL
Benign
0.024
Sift
Uncertain
0.012
D
Sift4G
Benign
0.11
T
Polyphen
0.017
B
Vest4
0.091
MVP
0.34
MPC
0.11
ClinPred
0.011
T
GERP RS
-0.65
Varity_R
0.066
gMVP
0.23

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.

Other links and lift over

dbSNP: rs374009361; hg19: chr5-112769552; COSMIC: COSV66815572; COSMIC: COSV66815572; API