Genetic Variant TSSK6:p.Tyr230* (chr19-19514738-A-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_032037.4(TSSK6):c.690T>A(p.Tyr230*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,450,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

TSSK6
NM_032037.4 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.89

Publications

0 publications found

Variant links:

Genes affected

TSSK6 (HGNC:30410): (testis specific serine kinase 6) This intronless gene encodes a member of the CAMK (calcium/calmodulin-dependent) serine/threonine protein kinase family. The encoded kinase has a broad expression pattern but is described as testis-specific due to effects on fertility. Male mice which lack the gene encoding a highly similar protein are sterile and have morphologically abnormal sperm. [provided by RefSeq, Jan 2012]

TSSK6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSSK6	NM_032037.4 link	c.690T>A	p.Tyr230*	stop_gained	Exon 1 of 1	ENST00000585580.4	NP_114426.1	Q9BXA6A0A024R7Q5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TSSK6	ENST00000585580.4 link	c.690T>A	p.Tyr230*	stop_gained	Exon 1 of 1	6	NM_032037.4	ENSP00000466477.1	Q9BXA6
TSSK6	ENST00000587522.3 link	n.690T>A		non_coding_transcript_exon_variant	Exon 1 of 2	2		ENSP00000466056.1	Q9BXA6
TSSK6	ENST00000602623.1 link	n.198T>A		non_coding_transcript_exon_variant	Exon 1 of 2	3		ENSP00000473413.1	R4GMZ2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.90e-7

AC:

AN:

1450190

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

721948

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33460

American (AMR)

AF:

0.00

AC:

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26094

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.00

AC:

AN:

86238

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42348

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111632

Other (OTH)

AF:

0.00

AC:

AN:

60276

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.50

BayesDel_noAF

Pathogenic

0.48

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Uncertain

0.30

Eigen_PC

Benign

0.15

FATHMM_MKL

Benign

0.74

PhyloP100

1.9

Vest4

0.24

GERP RS

4.0

Mutation Taster

=56/144

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over