20-2102054-C-A

Variant names:

• chr20-2102054-C-A
• rs1169017337
• NM_080836.4:c.173C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Moderate BS2

The NM_080836.4(STK35):​c.173C>A​(p.Ala58Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000365 in 1,371,408 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: STK35 NM_080836.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.335
• 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08232039).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

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.173C>A	p.Ala58Asp	missense	Exon 1 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.173C>A	p.Ala58Asp	missense	Exon 1 of 4	ENSP00000370891.3	Q8TDR2
	STK35	ENST00000926982.1		c.173C>A	p.Ala58Asp	missense	Exon 1 of 4	ENSP00000597041.1
	STK35	ENST00000968998.1		c.173C>A	p.Ala58Asp	missense	Exon 1 of 3	ENSP00000639057.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000365 AC: 5 AN: 1371408 Hom.: 0 Cov.: 30 AF XY: 0.00000592 AC XY: 4 AN XY: 675464

African (AFR) AF: 0.0000329 AC: 1 AN: 30356

American (AMR) AF: 0.00 AC: 0 AN: 35188

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24858

East Asian (EAS) AF: 0.00 AC: 0 AN: 35134

South Asian (SAS) AF: 0.00 AC: 0 AN: 78244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4370

European-Non Finnish (NFE) AF: 0.00000373 AC: 4 AN: 1072690

Other (OTH) AF: 0.00 AC: 0 AN: 57216

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	14
DANN	Benign	0.88
DEOGEN2	Benign	0.0040	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.22	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.34
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.046
Sift	Uncertain	0.010	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.012	B
Vest4		0.15
MutPred		0.30		Loss of helix (P = 0.0068)
MVP		0.22
MPC		1.5
ClinPred		0.14	T
GERP RS		0.94
PromoterAI		0.036	Neutral
Varity_R		0.20
gMVP		0.45
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs1169017337; hg19: chr20-2082700;