20-2165639-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000493263.1(STK35):c.*38-7665C>T variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,070 control chromosomes in the GnomAD database, including 6,145 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 0.27 (6145 hom., cov: 32)
• Consequence: STK35 ENST00000493263.1 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.663

Genes affected

STK35 (HGNC:16254): (serine/threonine kinase 35) The protein encoded by this gene is a kinase that is predominantly found in the nucleus. However, it can interact with PDLIM1/CLP-36 in the cytoplasm and localize to actin stress fibers. The encoded protein may be a regulator of actin stress fibers in nonmuscle cells. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK35	ENST00000493263.1	c.*38-7665C>T		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41537 AN: 151952 Hom.: 6143 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.0557

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.298

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.273 AC: 41565 AN: 152070 Hom.: 6145 Cov.: 32 AF XY: 0.270 AC XY: 20045 AN XY: 74332

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.0558

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.341

Gnomad4 OTH AF: 0.294

Alfa AF: 0.278 Hom.: 2984

Bravo AF: 0.262

Asia WGS AF: 0.117 AC: 408 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	12
Dann	Benign	0.32

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6047163; hg19: chr20-2146285;