rs7250893

chr19-19514738-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_032037.4(TSSK6):c.690T>C(p.Tyr230=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 1,602,324 control chromosomes in the GnomAD database, including 116,963 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.43 (15559 hom., cov: 34)
  • Exomes 𝑓: 0.37 (101404 hom.)
• Consequence: TSSK6 NM_032037.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.89

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP7: Synonymous conserved (PhyloP=1.89 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSSK6	NM_032037.4	c.690T>C	p.Tyr230=	synonymous_variant	1/1	ENST00000585580.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSSK6	ENST00000585580.4	c.690T>C	p.Tyr230=	synonymous_variant	1/1		NM_032037.4	P1
TSSK6	ENST00000587522.3	c.690T>C	p.Tyr230=	synonymous_variant, NMD_transcript_variant	1/2	2
TSSK6	ENST00000602623.1	c.198T>C	p.Tyr66=	synonymous_variant, NMD_transcript_variant	1/2	3

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65515 AN: 152074 Hom.: 15500 Cov.: 34

Gnomad AFR AF: 0.625

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.433

GnomAD3 exomes AF: 0.400 AC: 94789 AN: 236942 Hom.: 19954 AF XY: 0.400 AC XY: 51935 AN XY: 129990

Gnomad AFR exome AF: 0.627

Gnomad AMR exome AF: 0.453

Gnomad ASJ exome AF: 0.367

Gnomad EAS exome AF: 0.304

Gnomad SAS exome AF: 0.518

Gnomad FIN exome AF: 0.261

Gnomad NFE exome AF: 0.355

Gnomad OTH exome AF: 0.390

GnomAD4 exome AF: 0.368 AC: 533836 AN: 1450132 Hom.: 101404 Cov.: 73 AF XY: 0.371 AC XY: 268036 AN XY: 721916

Gnomad4 AFR exome AF: 0.635

Gnomad4 AMR exome AF: 0.452

Gnomad4 ASJ exome AF: 0.363

Gnomad4 EAS exome AF: 0.287

Gnomad4 SAS exome AF: 0.515

Gnomad4 FIN exome AF: 0.265

Gnomad4 NFE exome AF: 0.351

Gnomad4 OTH exome AF: 0.390

GnomAD4 genome AF: 0.431 AC: 65637 AN: 152192 Hom.: 15559 Cov.: 34 AF XY: 0.429 AC XY: 31891 AN XY: 74412

Gnomad4 AFR AF: 0.625

Gnomad4 AMR AF: 0.430

Gnomad4 ASJ AF: 0.356

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.517

Gnomad4 FIN AF: 0.250

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.439

Alfa AF: 0.374 Hom.: 7340

Bravo AF: 0.450

Asia WGS AF: 0.459 AC: 1595 AN: 3478

EpiCase AF: 0.360

EpiControl AF: 0.352

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	7.8
Dann	Benign	0.70

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: rs7250893; hg19: chr19-19625547; COSMIC: COSV53062657; COSMIC: COSV53062657;