5-113433915-C-T

Variant names:

• chr5-113433915-C-T
• NM_032028.4:c.925G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032028.4(TSSK1B):​c.925G>A​(p.Ala309Thr) 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. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A309V) has been classified 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: -0.322
• Publications: 0 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044202507).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032028.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSSK1B	NM_032028.4	MANE Select	c.925G>A	p.Ala309Thr	missense	Exon 1 of 1	NP_114417.1	Q9BXA7
	MCC	NM_001085377.2	MANE Select	c.171-48703G>A		intron	N/A	NP_001078846.2	P23508-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSSK1B	ENST00000390666.4	TSL:6 MANE Select	c.925G>A	p.Ala309Thr	missense	Exon 1 of 1	ENSP00000375081.3	Q9BXA7
	MCC	ENST00000408903.7	TSL:2 MANE Select	c.171-48703G>A		intron	N/A	ENSP00000386227.3	P23508-2
	ENSG00000232633	ENST00000416046.3	TSL:2	n.1312C>T		non_coding_transcript_exon	Exon 4 of 5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	7.3
DANN	Benign	0.84
DEOGEN2	Benign	0.030	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0018	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.32
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.042
Sift	Benign	0.26	T
Sift4G	Benign	0.28	T
Polyphen		0.0080	B
Vest4		0.038
MutPred		0.15		Gain of phosphorylation at A309 (P = 0.0092)
MVP		0.36
MPC		0.093
ClinPred		0.043	T
GERP RS		-0.22
Varity_R		0.035
gMVP		0.20
Mutation Taster		=100/0	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

hg19: chr5-112769612;