Variant 19-49739921-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021733.2(TSKS):c.1634C>A(p.Ala545Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,328 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TSKS
NM_021733.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.21

Variant links:

Genes affected

TSKS (HGNC:30719): (testis specific serine kinase substrate) This gene may play a role in testicular physiology, spermatogenesis or spermiogenesis. Expression of the encoded protein is highest in the testis and down-regulated in testicular cancer. The gene is localized to the region 19q13.3 among the related RAS viral oncogene homolog (RRAS) and interferon regulatory factor 3 (IRF3) genes, which are both involved in tumorigenesis pathways and progression. [provided by RefSeq, Jul 2008]

TSKS links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSKS	NM_021733.2 linkuse as main transcript	c.1634C>A	p.Ala545Asp	missense_variant	11/11	ENST00000246801.8	NP_068379.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSKS	ENST00000246801.8 linkuse as main transcript	c.1634C>A	p.Ala545Asp	missense_variant	11/11	1	NM_021733.2	ENSP00000246801	P1	Q9UJT2-1
TSKS	ENST00000358830.3 linkuse as main transcript	c.1034C>A	p.Ala345Asp	missense_variant	7/7	1		ENSP00000351691
TSKS	ENST00000599325.1 linkuse as main transcript	n.411C>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250472

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135376

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459328

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725514

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

Cov.:

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

Apr 09, 2024

The c.1634C>A (p.A545D) alteration is located in exon 11 (coding exon 11) of the TSKS gene. This alteration results from a C to A substitution at nucleotide position 1634, causing the alanine (A) at amino acid position 545 to be replaced by an aspartic acid (D). 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

0.25

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

0.11

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.096

T;.

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.74

T;T

M_CAP

Benign

0.058

MetaRNN

Uncertain

0.60

D;D

MetaSVM

Benign

-0.85

MutationTaster

Benign

0.93

D;D

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-2.8

D;D

REVEL

Benign

0.25

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.83

MutPred

0.12

Gain of relative solvent accessibility (P = 0.0215);.;

MVP

0.23

MPC

0.98

ClinPred

0.99

GERP RS

5.4

Varity_R

0.79

gMVP

0.46

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