Variant chr5-147361525-A-G 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.571A>G(p.Met191Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M191I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

STK32A
NM_001112724.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.03

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=0.37828124).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK32A	NM_001112724.2 linkuse as main transcript	c.571A>G	p.Met191Val	missense_variant	8/13	ENST00000397936.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK32A	ENST00000397936.8 linkuse as main transcript	c.571A>G	p.Met191Val	missense_variant	8/13	5	NM_001112724.2	P1	Q8WU08-1
STK32A	ENST00000398523.3 linkuse as main transcript	c.571A>G	p.Met191Val	missense_variant	8/14	2
STK32A	ENST00000306304.10 linkuse as main transcript	n.904A>G		non_coding_transcript_exon_variant	8/11	2
STK32A	ENST00000648628.1 linkuse as main transcript	c.565A>G	p.Met189Val	missense_variant, NMD_transcript_variant	9/15

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459866

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725990

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

May 14, 2024

The c.571A>G (p.M191V) alteration is located in exon 8 (coding exon 7) of the STK32A gene. This alteration results from a A to G substitution at nucleotide position 571, causing the methionine (M) at amino acid position 191 to be replaced by a valine (V). 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

0.15

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.040

CADD

Benign

DANN

Benign

0.76

DEOGEN2

Benign

0.019

T;T

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.96

D;D

M_CAP

Benign

0.012

MetaRNN

Benign

0.38

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-1.1

N;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.52

PROVEAN

Benign

0.97

N;N

REVEL

Benign

0.21

Sift

Benign

0.62

T;T

Sift4G

Benign

0.89

T;T

Polyphen

0.14

B;B

Vest4

0.79

MutPred

0.47

Loss of disorder (P = 0.0623);Loss of disorder (P = 0.0623);

MVP

0.40

MPC

0.14

ClinPred

0.76

GERP RS

5.5

Varity_R

0.33

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over