NM_001282547.2:c.1156G>A

Variant names:

• chr1-36341907-C-T
• rs756696476
• NM_001282547.2:c.1156G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001282547.2(STK40):​c.1156G>A​(p.Ala386Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A386P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: STK40 NM_001282547.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.49
• Publications: 0 publications found

Genes affected

STK40 (HGNC:21373): (serine/threonine kinase 40) Predicted to enable ATP binding activity; protein serine kinase activity; and protein serine/threonine kinase activity. Predicted to be involved in protein phosphorylation. Predicted to act upstream of or within several processes, including glycogen metabolic process; lung development; and respiratory system process. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK40	NM_001282547.2	c.1156G>A	p.Ala386Thr	missense_variant	Exon 11 of 11	ENST00000373132.4	NP_001269476.1
STK40	NM_001282546.2	c.1171G>A	p.Ala391Thr	missense_variant	Exon 11 of 11		NP_001269475.1
STK40	NM_032017.3	c.1156G>A	p.Ala386Thr	missense_variant	Exon 12 of 12		NP_114406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK40	ENST00000373132.4	c.1156G>A	p.Ala386Thr	missense_variant	Exon 11 of 11	1	NM_001282547.2	ENSP00000362224.4
STK40	ENST00000373130.7	c.1171G>A	p.Ala391Thr	missense_variant	Exon 11 of 11	1		ENSP00000362222.3
STK40	ENST00000373129.7	c.1156G>A	p.Ala386Thr	missense_variant	Exon 12 of 12	1		ENSP00000362221.3
STK40	ENST00000359297.6	c.*1292G>A		3_prime_UTR_variant	Exon 9 of 9	2		ENSP00000352245.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 249288 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.058	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T;.;T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	.;D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.43	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.90	L;.;L
PhyloP100		7.5
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.52	N;N;N
REVEL	Benign	0.22
Sift	Benign	0.060	T;D;T
Sift4G	Benign	0.29	T;T;T
Polyphen		0.0040	B;P;B
Vest4		0.63
MutPred		0.23		Loss of phosphorylation at S391 (P = 0.1879);.;Loss of phosphorylation at S391 (P = 0.1879);
MVP		0.44
MPC		0.42
ClinPred		0.74	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.10
gMVP		0.42
Mutation Taster		=56/44	polymorphism

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

Other links and lift over

dbSNP: rs756696476; hg19: chr1-36807508;