rs56405327

Variant names:

• chr1-36341962-C-G
• rs56405327
• NM_001282547.2:c.1101G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-36341962-C-G
• chr1-36341962-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001282547.2(STK40):​c.1101G>C​(p.Thr367Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,742 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. Synonymous variant affecting the same amino acid position (i.e. T367T) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: STK40 NM_001282547.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -7.35
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP7: Synonymous conserved (PhyloP=-7.35 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK40	NM_001282547.2	c.1101G>C	p.Thr367Thr	synonymous_variant	Exon 11 of 11	ENST00000373132.4	NP_001269476.1
STK40	NM_001282546.2	c.1116G>C	p.Thr372Thr	synonymous_variant	Exon 11 of 11		NP_001269475.1
STK40	NM_032017.3	c.1101G>C	p.Thr367Thr	synonymous_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.1101G>C	p.Thr367Thr	synonymous_variant	Exon 11 of 11	1	NM_001282547.2	ENSP00000362224.4
STK40	ENST00000373130.7	c.1116G>C	p.Thr372Thr	synonymous_variant	Exon 11 of 11	1		ENSP00000362222.3
STK40	ENST00000373129.7	c.1101G>C	p.Thr367Thr	synonymous_variant	Exon 12 of 12	1		ENSP00000362221.3
STK40	ENST00000359297.6	c.*1237G>C		3_prime_UTR_variant	Exon 9 of 9	2		ENSP00000352245.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460742 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726640

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44588

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39658

South Asian (SAS) AF: 0.00 AC: 0 AN: 86146

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53314

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111474

Other (OTH) AF: 0.00 AC: 0 AN: 60318

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.0090
DANN	Benign	0.62
PhyloP100		-7.3
Mutation Taster		=99/1	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: rs56405327; hg19: chr1-36807563;