chr5-147324025-C-A

Position:

• chr5-147324025-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001112724.2(STK32A):​c.388C>A​(p.Leu130Met) 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 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 (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: STK32A NM_001112724.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.50

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 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=0.37216243).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK32A	NM_001112724.2	c.388C>A	p.Leu130Met	missense_variant	5/13	ENST00000397936.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK32A	ENST00000397936.8	c.388C>A	p.Leu130Met	missense_variant	5/13	5	NM_001112724.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 16, 2021

The c.388C>A (p.L130M) alteration is located in exon 5 (coding exon 4) of the STK32A gene. This alteration results from a C to A substitution at nucleotide position 388, causing the leucine (L) at amino acid position 130 to be replaced by a methionine (M). 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	0.16
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.041	T;.;T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.78	T;T;T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.37	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;L;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.60	N;.;N
REVEL	Benign	0.12
Sift	Benign	0.27	T;.;T
Sift4G	Benign	0.25	T;T;T
Polyphen		1.0	D;P;D
Vest4		0.50
MutPred		0.63		Gain of MoRF binding (P = 0.6742);Gain of MoRF binding (P = 0.6742);Gain of MoRF binding (P = 0.6742);
MVP		0.31
MPC		0.39
ClinPred		0.88	D
GERP RS		5.5
Varity_R		0.38
gMVP		0.42

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-146703588;