rs55940513

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_032028.4(TSSK1B):​c.697G>C​(p.Val233Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00286 in 1,614,144 control chromosomes in the GnomAD database, including 96 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V233I) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.0048 ( 7 hom., cov: 32)
Exomes š‘“: 0.0027 ( 89 hom. )

Consequence

TSSK1B
NM_032028.4 missense

Scores

1
17

Clinical Significance

Not reported in ClinVar

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]
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 Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.002570361).
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00482 (734/152270) while in subpopulation EAS AF= 0.0424 (219/5164). AF 95% confidence interval is 0.0378. There are 7 homozygotes in gnomad4. There are 403 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TSSK1BNM_032028.4 linkc.697G>C p.Val233Leu missense_variant Exon 1 of 1 ENST00000390666.4 NP_114417.1 Q9BXA7A0ZT98
MCCNM_001085377.2 linkc.171-48931G>C intron_variant Intron 1 of 18 ENST00000408903.7 NP_001078846.2 P23508-2
LOC107986366XR_001742459.2 linkn.179+5364C>G intron_variant Intron 2 of 4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TSSK1BENST00000390666.4 linkc.697G>C p.Val233Leu missense_variant Exon 1 of 1 6 NM_032028.4 ENSP00000375081.3 Q9BXA7
MCCENST00000408903.7 linkc.171-48931G>C intron_variant Intron 1 of 18 2 NM_001085377.2 ENSP00000386227.3 P23508-2
ENSG00000232633ENST00000416046.2 linkn.1540C>G non_coding_transcript_exon_variant Exon 4 of 5 2

Frequencies

GnomAD3 genomes
AF:
0.00480
AC:
731
AN:
152152
Hom.:
7
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00183
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0421
Gnomad SAS
AF:
0.00311
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000118
Gnomad OTH
AF:
0.00621
GnomAD3 exomes
AF:
0.00869
AC:
2184
AN:
251388
Hom.:
50
AF XY:
0.00727
AC XY:
988
AN XY:
135872
show subpopulations
Gnomad AFR exome
AF:
0.00148
Gnomad AMR exome
AF:
0.0328
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0490
Gnomad SAS exome
AF:
0.00209
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000791
Gnomad OTH exome
AF:
0.00881
GnomAD4 exome
AF:
0.00265
AC:
3881
AN:
1461874
Hom.:
89
Cov.:
31
AF XY:
0.00255
AC XY:
1856
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.000896
Gnomad4 AMR exome
AF:
0.0314
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0465
Gnomad4 SAS exome
AF:
0.00238
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000504
Gnomad4 OTH exome
AF:
0.00553
GnomAD4 genome
AF:
0.00482
AC:
734
AN:
152270
Hom.:
7
Cov.:
32
AF XY:
0.00541
AC XY:
403
AN XY:
74446
show subpopulations
Gnomad4 AFR
AF:
0.00183
Gnomad4 AMR
AF:
0.0263
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0424
Gnomad4 SAS
AF:
0.00311
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00615
Alfa
AF:
0.00137
Hom.:
2
Bravo
AF:
0.00693
ESP6500AA
AF:
0.00114
AC:
5
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.00718
AC:
872
Asia WGS
AF:
0.0340
AC:
119
AN:
3478
EpiCase
AF:
0.000218
EpiControl
AF:
0.000178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.36
BayesDel_addAF
Benign
-0.62
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
5.1
DANN
Benign
0.67
DEOGEN2
Benign
0.096
T
Eigen
Benign
-1.8
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.0038
N
LIST_S2
Benign
0.72
T
MetaRNN
Benign
0.0026
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.52
N
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-1.6
N
REVEL
Benign
0.066
Sift
Benign
0.25
T
Sift4G
Benign
0.32
T
Polyphen
0.019
B
Vest4
0.034
MVP
0.34
MPC
0.11
ClinPred
0.0059
T
GERP RS
-0.54
Varity_R
0.11
gMVP
0.25

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: rs55940513; hg19: chr5-112769840; API