chr5-113434295-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_032028.4(TSSK1B):​c.545C>T​(p.Ala182Val) variant causes a missense change. The variant allele was found at a frequency of 0.000039 in 1,613,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 32)
Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

TSSK1B
NM_032028.4 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.13
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.40575397).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TSSK1BNM_032028.4 linkuse as main transcriptc.545C>T p.Ala182Val missense_variant 1/1 ENST00000390666.4 NP_114417.1 Q9BXA7A0ZT98
MCCNM_001085377.2 linkuse as main transcriptc.171-49083C>T intron_variant ENST00000408903.7 NP_001078846.2 P23508-2
LOC107986366XR_001742459.2 linkuse as main transcriptn.179+5516G>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TSSK1BENST00000390666.4 linkuse as main transcriptc.545C>T p.Ala182Val missense_variant 1/16 NM_032028.4 ENSP00000375081.3 Q9BXA7
MCCENST00000408903.7 linkuse as main transcriptc.171-49083C>T intron_variant 2 NM_001085377.2 ENSP00000386227.3 P23508-2
ENSG00000232633ENST00000416046.2 linkuse as main transcriptn.1692G>A non_coding_transcript_exon_variant 4/52

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152172
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000359
AC:
9
AN:
251010
Hom.:
0
AF XY:
0.0000442
AC XY:
6
AN XY:
135712
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000352
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000397
AC:
58
AN:
1461772
Hom.:
0
Cov.:
31
AF XY:
0.0000440
AC XY:
32
AN XY:
727188
show subpopulations
Gnomad4 AFR exome
AF:
0.000149
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000162
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000324
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152172
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000823
Hom.:
0
Bravo
AF:
0.0000453
ExAC
AF:
0.0000412
AC:
5
Asia WGS
AF:
0.00173
AC:
6
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 submitterclinical testingAmbry GeneticsJun 27, 2022The c.545C>T (p.A182V) alteration is located in exon 1 (coding exon 1) of the TSSK1B gene. This alteration results from a C to T substitution at nucleotide position 545, causing the alanine (A) at amino acid position 182 to be replaced by a valine (V). 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
0.16
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.31
T
Eigen
Benign
-0.0039
Eigen_PC
Benign
-0.12
FATHMM_MKL
Benign
0.65
D
LIST_S2
Pathogenic
0.98
D
M_CAP
Benign
0.0022
T
MetaRNN
Benign
0.41
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.49
N
MutationTaster
Benign
1.0
D;N
PrimateAI
Benign
0.33
T
PROVEAN
Uncertain
-3.9
D
REVEL
Benign
0.22
Sift
Uncertain
0.0080
D
Sift4G
Uncertain
0.0040
D
Polyphen
0.99
D
Vest4
0.30
MVP
0.38
MPC
0.48
ClinPred
0.65
D
GERP RS
1.2
Varity_R
0.42
gMVP
0.56

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs755285810; hg19: chr5-112769992; COSMIC: COSV66816243; COSMIC: COSV66816243; API