5-147361524-G-C

Position:

• chr5-147361524-G-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001112724.2(STK32A):​c.570G>C​(p.Glu190Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: STK32A NM_001112724.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.621

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.979

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK32A	NM_001112724.2	c.570G>C	p.Glu190Asp	missense_variant	8/13	ENST00000397936.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK32A	ENST00000397936.8	c.570G>C	p.Glu190Asp	missense_variant	8/13	5	NM_001112724.2	P1
STK32A	ENST00000398523.3	c.570G>C	p.Glu190Asp	missense_variant	8/14	2
STK32A	ENST00000306304.10	n.903G>C		non_coding_transcript_exon_variant	8/11	2
STK32A	ENST00000648628.1	c.564G>C	p.Glu188Asp	missense_variant, NMD_transcript_variant	9/15

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2022

STK32A: PM2, PS2:Supporting -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.20
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T;T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Pathogenic	0.99	D;D
M_CAP	Uncertain	0.097	D
MetaRNN	Pathogenic	0.98	D;D
MetaSVM	Uncertain	0.17	D
MutationAssessor	Pathogenic	3.4	M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Uncertain	0.55
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.98	D;D
Vest4		0.86
MutPred		0.94		Loss of catalytic residue at E190 (P = 0.0977);Loss of catalytic residue at E190 (P = 0.0977);
MVP		0.78
MPC		0.30
ClinPred		0.99	D
GERP RS		3.6
Varity_R		0.78
gMVP		0.92

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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.

Other links and lift over

hg19: chr5-146741087;