rs55940513

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr5-113434143-C-G
• chr5-113434143-C-T

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt. 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

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

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• 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	ENST00000416046.2	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

GnomAD3 exomes AF: 0.00869 AC: 2184 AN: 251388 Hom.: 50 AF XY: 0.00727 AC XY: 988 AN XY: 135872

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 SAS exome AF: 0.00209

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

Gnomad4 AFR exome AF: 0.000896

Gnomad4 AMR exome AF: 0.0314

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0465

Gnomad4 SAS exome AF: 0.00238

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000504

Gnomad4 OTH exome AF: 0.00553

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

Gnomad4 AFR AF: 0.00183

Gnomad4 AMR AF: 0.0263

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0424

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00615

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
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

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

LitVar

Other links and lift over

dbSNP: rs55940513; hg19: chr5-112769840;