dbSNP rs779824878: STK32A:p.Met337Lys (chr5-147375196-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001112724.2(STK32A):c.1010T>A(p.Met337Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

STK32A
NM_001112724.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0160

Publications

0 publications found

Variant links:

Genes affected

STK32A (HGNC:28317): (serine/threonine kinase 32A) Predicted to enable protein serine/threonine kinase activity. Predicted to be involved in intracellular signal transduction and peptidyl-serine phosphorylation. Predicted to be located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

STK32A links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.048206687).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK32A	NM_001112724.2 link	c.1010T>A	p.Met337Lys	missense_variant	Exon 11 of 13	ENST00000397936.8	NP_001106195.1	Q8WU08-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK32A	ENST00000397936.8 link	c.1010T>A	p.Met337Lys	missense_variant	Exon 11 of 13	5	NM_001112724.2	ENSP00000381030.3		Q8WU08-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1458840

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725386

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33394

American (AMR)

AF:

0.00

AC:

AN:

44388

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26024

East Asian (EAS)

AF:

0.0000505

AC:

AN:

39608

South Asian (SAS)

AF:

0.00

AC:

AN:

85456

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53314

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110654

Other (OTH)

AF:

0.00

AC:

AN:

60244

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000166

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 17, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1010T>A (p.M337K) alteration is located in exon 11 (coding exon 10) of the STK32A gene. This alteration results from a T to A substitution at nucleotide position 1010, causing the methionine (M) at amino acid position 337 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.099

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.63

DEOGEN2

Benign

0.0080

T;T

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.75

T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.048

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;.

PhyloP100

0.016

PrimateAI

Benign

0.41

PROVEAN

Benign

0.22

N;N

REVEL

Benign

0.090

Sift

Benign

0.93

T;T

Sift4G

Benign

0.92

T;T

Polyphen

0.0070

B;B

Vest4

0.39

MutPred

0.34

Gain of solvent accessibility (P = 0.0016);Gain of solvent accessibility (P = 0.0016);

MVP

0.60

MPC

0.099

ClinPred

0.066

GERP RS

1.8

Varity_R

0.23

gMVP

0.32

Mutation Taster

=89/11

polymorphism

(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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rs779824878

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over