Variant 5-147370747-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001112724.2(STK32A):c.754G>A(p.Glu252Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000548 in 1,459,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

STK32A
NM_001112724.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.17

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 made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32549652).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK32A	NM_001112724.2 linkuse as main transcript	c.754G>A	p.Glu252Lys	missense_variant	9/13	ENST00000397936.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK32A	ENST00000397936.8 linkuse as main transcript	c.754G>A	p.Glu252Lys	missense_variant	9/13	5	NM_001112724.2	P1	Q8WU08-1
STK32A	ENST00000398523.3 linkuse as main transcript	c.754G>A	p.Glu252Lys	missense_variant	9/14	2
STK32A	ENST00000306304.10 linkuse as main transcript	n.1087G>A		non_coding_transcript_exon_variant	9/11	2
STK32A	ENST00000648628.1 linkuse as main transcript	c.748G>A	p.Glu250Lys	missense_variant, NMD_transcript_variant	10/15

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000805

AC:

AN:

248402

Hom.:

AF XY:

0.00000741

AC XY:

AN XY:

134980

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000548

AC:

AN:

1459510

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726100

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000498

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 22, 2023

The c.754G>A (p.E252K) alteration is located in exon 9 (coding exon 8) of the STK32A gene. This alteration results from a G to A substitution at nucleotide position 754, causing the glutamic acid (E) at amino acid position 252 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

0.14

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.045

T;T

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.019

MetaRNN

Benign

0.33

T;T

MetaSVM

Benign

-0.54

MutationAssessor

Benign

1.5

L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.21

Sift

Benign

0.26

T;T

Sift4G

Benign

0.47

T;T

Polyphen

0.73

P;B

Vest4

0.46

MutPred

0.67

Gain of MoRF binding (P = 0.028);Gain of MoRF binding (P = 0.028);

MVP

0.81

MPC

0.25

ClinPred

0.77

GERP RS

5.5

Varity_R

0.45

gMVP

0.66

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over