5-113434143-C-G

Variant names:

• chr5-113434143-C-G
• rs55940513
• NM_032028.4:c.697G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

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. 15/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. V233I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0048 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (89 hom.)
• Consequence: TSSK1B NM_032028.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.495
• Publications: 7 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: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSSK1B	NM_032028.4	c.697G>C	p.Val233Leu	missense_variant	Exon 1 of 1	ENST00000390666.4	NP_114417.1
MCC	NM_001085377.2	c.171-48931G>C		intron_variant	Intron 1 of 18	ENST00000408903.7	NP_001078846.2
LOC107986366	XR_001742459.2	n.179+5364C>G		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSSK1B	ENST00000390666.4	c.697G>C	p.Val233Leu	missense_variant	Exon 1 of 1	6	NM_032028.4	ENSP00000375081.3
MCC	ENST00000408903.7	c.171-48931G>C		intron_variant	Intron 1 of 18	2	NM_001085377.2	ENSP00000386227.3
ENSG00000232633	ENST00000416046.3	n.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

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

GnomAD2 exomes AF: 0.00869 AC: 2184 AN: 251388 AF XY: 0.00727

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 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

African (AFR) AF: 0.000896 AC: 30 AN: 33480

American (AMR) AF: 0.0314 AC: 1406 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0465 AC: 1848 AN: 39700

South Asian (SAS) AF: 0.00238 AC: 205 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.0000504 AC: 56 AN: 1111998

Other (OTH) AF: 0.00553 AC: 334 AN: 60392

GnomAD4 genome AF: 0.00482 AC: 734 AN: 152270 Hom.: 7 Cov.: 32 AF XY: 0.00541 AC XY: 403 AN XY: 74446

African (AFR) AF: 0.00183 AC: 76 AN: 41562

American (AMR) AF: 0.0263 AC: 403 AN: 15304

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

East Asian (EAS) AF: 0.0424 AC: 219 AN: 5164

South Asian (SAS) AF: 0.00311 AC: 15 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68018

Other (OTH) AF: 0.00615 AC: 13 AN: 2114

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
PhyloP100		0.49
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
Mutation Taster		=99/1	polymorphism (auto)

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: rs55940513; hg19: chr5-112769840; COSMIC: COSV107484268; COSMIC: COSV107484268;