rs980466082

Variant names:

• chr20-2102783-C-G
• rs980466082
• NM_080836.4:c.310C>G

Your query was ambiguous. Multiple possible variants found:

• chr20-2102783-C-G
• chr20-2102783-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_080836.4(STK35):​c.310C>G​(p.Pro104Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P104S) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: STK35 NM_080836.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.659
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13072786).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080836.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK35	NM_080836.4	MANE Select	c.310C>G	p.Pro104Ala	missense	Exon 2 of 4	NP_543026.2	Q8TDR2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK35	ENST00000381482.8	TSL:5 MANE Select	c.310C>G	p.Pro104Ala	missense	Exon 2 of 4	ENSP00000370891.3	Q8TDR2
	STK35	ENST00000926982.1		c.310C>G	p.Pro104Ala	missense	Exon 2 of 4	ENSP00000597041.1
	STK35	ENST00000968998.1		c.310C>G	p.Pro104Ala	missense	Exon 2 of 3	ENSP00000639057.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152226 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152226 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74384

African (AFR) AF: 0.00 AC: 0 AN: 41468

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2094

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.0048	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.53	T
M_CAP	Pathogenic	0.59	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.66
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.059
Sift	Benign	0.047	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.0	B
Vest4		0.21
MutPred		0.22		Loss of glycosylation at P104 (P = 0.0235)
MVP		0.23
MPC		1.0
ClinPred		0.10	T
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.068
gMVP		0.25
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs980466082; hg19: chr20-2083429;