rs756696476

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-36341907-C-A
• chr1-36341907-C-G
• chr1-36341907-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001282547.2(STK40):​c.1156G>T​(p.Ala386Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38831088).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK40	NM_001282547.2	c.1156G>T	p.Ala386Ser	missense_variant	Exon 11 of 11	ENST00000373132.4	NP_001269476.1
STK40	NM_001282546.2	c.1171G>T	p.Ala391Ser	missense_variant	Exon 11 of 11		NP_001269475.1
STK40	NM_032017.3	c.1156G>T	p.Ala386Ser	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>T	p.Ala386Ser	missense_variant	Exon 11 of 11	1	NM_001282547.2	ENSP00000362224.4
STK40	ENST00000373130.7	c.1171G>T	p.Ala391Ser	missense_variant	Exon 11 of 11	1		ENSP00000362222.3
STK40	ENST00000373129.7	c.1156G>T	p.Ala386Ser	missense_variant	Exon 12 of 12	1		ENSP00000362221.3
STK40	ENST00000359297.6	c.*1292G>T		3_prime_UTR_variant	Exon 9 of 9	2		ENSP00000352245.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461662 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727148

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53358

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5714

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111952

Other (OTH) AF: 0.00 AC: 0 AN: 60374

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.016	T;.;T
Eigen	Benign	0.075
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	.;D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.39	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.90	L;.;L
PhyloP100		7.5
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.070	N;N;N
REVEL	Benign	0.22
Sift	Benign	0.15	T;T;T
Sift4G	Benign	0.68	T;T;T
Polyphen		0.039	B;P;B
Vest4		0.60
MutPred		0.32		Gain of disorder (P = 0.033);.;Gain of disorder (P = 0.033);
MVP		0.47
MPC		0.39
ClinPred		0.67	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.28
Mutation Taster		=55/45	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;