chr19-49745313-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The ENST00000246801.8(TSKS):c.1076G>A(p.Gly359Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000536 in 1,603,996 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000056 ( 0 hom. )
Consequence
TSKS
ENST00000246801.8 missense
ENST00000246801.8 missense
Scores
3
10
6
Clinical Significance
Conservation
PhyloP100: 3.46
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]
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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 | c.1076G>A | p.Gly359Asp | missense_variant | 7/11 | ENST00000246801.8 | NP_068379.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TSKS | ENST00000246801.8 | c.1076G>A | p.Gly359Asp | missense_variant | 7/11 | 1 | NM_021733.2 | ENSP00000246801.2 | ||
TSKS | ENST00000358830.3 | c.476G>A | p.Gly159Asp | missense_variant | 3/7 | 1 | ENSP00000351691.2 |
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152212Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000424 AC: 10AN: 235634Hom.: 0 AF XY: 0.0000465 AC XY: 6AN XY: 129132
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GnomAD4 exome AF: 0.0000558 AC: 81AN: 1451784Hom.: 0 Cov.: 31 AF XY: 0.0000498 AC XY: 36AN XY: 722536
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GnomAD4 genome AF: 0.0000328 AC: 5AN: 152212Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74354
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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 | Jan 03, 2024 | The c.1076G>A (p.G359D) alteration is located in exon 7 (coding exon 7) of the TSKS gene. This alteration results from a G to A substitution at nucleotide position 1076, causing the glycine (G) at amino acid position 359 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Benign
Sift
Pathogenic
D;D
Sift4G
Uncertain
D;D
Polyphen
D;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at