rs771385288

Variant names:

• chr5-113433824-G-A
• rs771385288
• NM_032028.4:c.1016C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-113433824-G-A
• chr5-113433824-G-C
• chr5-113433824-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_032028.4(TSSK1B):​c.1016C>T​(p.Ser339Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,613,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: TSSK1B NM_032028.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.227
• Publications: 1 publications found

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]

ENSG00000232633 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.037265092).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSSK1B	NM_032028.4	c.1016C>T	p.Ser339Leu	missense_variant	Exon 1 of 1	ENST00000390666.4	NP_114417.1
MCC	NM_001085377.2	c.171-48612C>T		intron_variant	Intron 1 of 18	ENST00000408903.7	NP_001078846.2
LOC107986366	XR_001742459.2	n.179+5045G>A		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSSK1B	ENST00000390666.4	c.1016C>T	p.Ser339Leu	missense_variant	Exon 1 of 1	6	NM_032028.4	ENSP00000375081.3
MCC	ENST00000408903.7	c.171-48612C>T		intron_variant	Intron 1 of 18	2	NM_001085377.2	ENSP00000386227.3
ENSG00000232633	ENST00000416046.3	n.1221G>A		non_coding_transcript_exon_variant	Exon 4 of 5	2

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 152216 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

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

GnomAD2 exomes AF: 0.0000362 AC: 9 AN: 248902 AF XY: 0.0000518

Gnomad AFR exome AF: 0.000388

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000171 AC: 25 AN: 1461632 Hom.: 0 Cov.: 30 AF XY: 0.0000220 AC XY: 16 AN XY: 727098

African (AFR) AF: 0.000329 AC: 11 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000989 AC: 11 AN: 1111842

Other (OTH) AF: 0.0000166 AC: 1 AN: 60370

GnomAD4 genome AF: 0.000112 AC: 17 AN: 152216 Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8 AN XY: 74352

African (AFR) AF: 0.000410 AC: 17 AN: 41464

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68050

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000987 Hom.: 0

Bravo AF: 0.000102

ExAC AF: 0.0000414 AC: 5

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1016C>T (p.S339L) 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 1016, causing the serine (S) at amino acid position 339 to be replaced by a leucine (L). 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	0.081
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	5.4
DANN	Benign	0.68
DEOGEN2	Benign	0.066	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0033	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.23
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.064
Sift	Benign	0.33	T
Sift4G	Benign	0.077	T
Polyphen		0.0	B
Vest4		0.12
MVP		0.42
MPC		0.084
ClinPred		0.0076	T
GERP RS		0.90
Varity_R		0.043
gMVP		0.24
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs771385288; hg19: chr5-112769521;