5-113433840-G-T

Position:

• chr5-113433840-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032028.4(TSSK1B):​c.1000C>A​(p.Gln334Lys) 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. 16/21 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.304

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09192002).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSSK1B	NM_032028.4	c.1000C>A	p.Gln334Lys	missense_variant	1/1	ENST00000390666.4	NP_114417.1
MCC	NM_001085377.2	c.171-48628C>A		intron_variant		ENST00000408903.7	NP_001078846.2
LOC107986366	XR_001742459.2	n.179+5061G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSSK1B	ENST00000390666.4	c.1000C>A	p.Gln334Lys	missense_variant	1/1		NM_032028.4	ENSP00000375081	P1
MCC	ENST00000408903.7	c.171-48628C>A		intron_variant		2	NM_001085377.2	ENSP00000386227	P1
	ENST00000416046.2	n.1237G>T		non_coding_transcript_exon_variant	4/5	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2023

The c.1000C>A (p.Q334K) alteration is located in exon 1 (coding exon 1) of the TSSK1B gene. This alteration results from a C to A substitution at nucleotide position 1000, causing the glutamine (Q) at amino acid position 334 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	0.071
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	2.6
DANN	Benign	0.47
DEOGEN2	Benign	0.042	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.038
Sift	Benign	0.28	T
Sift4G	Benign	0.77	T
Polyphen		0.0020	B
Vest4		0.16
MutPred		0.28		Gain of ubiquitination at Q334 (P = 0.0031);
MVP		0.37
MPC		0.13
ClinPred		0.069	T
GERP RS		0.90
Varity_R		0.090
gMVP		0.18

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: chr5-112769537;