Variant 1-32363777-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000373534.4(TSSK3):c.328C>T(p.Arg110Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,614,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

TSSK3
ENST00000373534.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.302

Variant links:

Genes affected

TSSK3 (HGNC:15473): (testis specific serine kinase 3) This gene encodes a kinase expressed exclusively in the testis that is thought to play a role in either germ cell differentiation or mature sperm function. [provided by RefSeq, Jul 2008]

TSSK3 links:

FAM229A (HGNC:):

FAM229A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28254092).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSSK3	NM_052841.4 linkuse as main transcript	c.328C>T	p.Arg110Trp	missense_variant	2/2	ENST00000373534.4	NP_443073.1	Q96PN8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TSSK3	ENST00000373534.4 linkuse as main transcript	c.328C>T	p.Arg110Trp	missense_variant	2/2	1	NM_052841.4	ENSP00000362634.3	Q96PN8
FAM229A	ENST00000416512.1 linkuse as main transcript	n.447G>A		non_coding_transcript_exon_variant	1/2	1
TSSK3	ENST00000574315.1 linkuse as main transcript	c.103C>T	p.Arg35Trp	missense_variant, splice_region_variant	2/2	3		ENSP00000459187.1	I3L1X4
FAM229A	ENST00000415596.1 linkuse as main transcript	n.204+298G>A		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251426

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000889

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152354

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.0000330

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 10, 2022

The c.328C>T (p.R110W) alteration is located in exon 2 (coding exon 2) of the TSSK3 gene. This alteration results from a C to T substitution at nucleotide position 328, causing the arginine (R) at amino acid position 110 to be replaced by a tryptophan (W). 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

0.16

BayesDel_addAF

Benign

-0.080

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.15

.;T

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.15

FATHMM_MKL

Benign

0.37

LIST_S2

Uncertain

0.88

D;T

M_CAP

Benign

0.034

MetaRNN

Benign

0.28

T;T

MetaSVM

Benign

-0.49

MutationAssessor

Benign

1.4

.;L

MutationTaster

Benign

0.91

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-3.6

.;D

REVEL

Uncertain

0.34

Sift

Uncertain

0.017

.;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.96

.;D

Vest4

0.53

MVP

0.67

MPC

0.17

ClinPred

0.93

GERP RS

4.5

Varity_R

0.27

gMVP

0.51

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over