5-113434101-C-T

Variant summary

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

The NM_032028.4(TSSK1B):​c.739G>A​(p.Asp247Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

TSSK1B
NM_032028.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.45
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=0.39332163).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TSSK1BNM_032028.4 linkc.739G>A p.Asp247Asn missense_variant Exon 1 of 1 ENST00000390666.4 NP_114417.1 Q9BXA7A0ZT98
MCCNM_001085377.2 linkc.171-48889G>A intron_variant Intron 1 of 18 ENST00000408903.7 NP_001078846.2 P23508-2
LOC107986366XR_001742459.2 linkn.179+5322C>T intron_variant Intron 2 of 4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TSSK1BENST00000390666.4 linkc.739G>A p.Asp247Asn missense_variant Exon 1 of 1 6 NM_032028.4 ENSP00000375081.3 Q9BXA7
MCCENST00000408903.7 linkc.171-48889G>A intron_variant Intron 1 of 18 2 NM_001085377.2 ENSP00000386227.3 P23508-2
ENSG00000232633ENST00000416046.2 linkn.1498C>T non_coding_transcript_exon_variant Exon 4 of 5 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 10, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.739G>A (p.D247N) 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 739, causing the aspartic acid (D) at amino acid position 247 to be replaced by an asparagine (N). 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
0.17
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Benign
0.20
T
Eigen
Benign
-0.84
Eigen_PC
Benign
-0.90
FATHMM_MKL
Benign
0.59
D
LIST_S2
Uncertain
0.88
D
M_CAP
Benign
0.0033
T
MetaRNN
Benign
0.39
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.5
L
PrimateAI
Benign
0.39
T
PROVEAN
Uncertain
-2.6
D
REVEL
Benign
0.076
Sift
Benign
0.089
T
Sift4G
Benign
0.088
T
Polyphen
0.096
B
Vest4
0.15
MutPred
0.62
Loss of phosphorylation at Y250 (P = 0.0788);
MVP
0.29
MPC
0.28
ClinPred
0.61
D
GERP RS
0.83
Varity_R
0.12
gMVP
0.36

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-112769798; COSMIC: COSV66816007; COSMIC: COSV66816007; API