1-36341962-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001282547.2(STK40):​c.1101G>A​(p.Thr367Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0056 in 1,613,106 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (57 hom., cov: 33)
  • Exomes 𝑓: 0.0044 (57 hom.)
• Consequence: STK40 NM_001282547.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -7.35
• Publications: 5 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 1-36341962-C-T is Benign according to our data. Variant chr1-36341962-C-T is described in ClinVar as [Benign]. Clinvar id is 783933.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-7.35 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0509 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0172 AC: 2613 AN: 152258 Hom.: 59 Cov.: 33

Gnomad AFR AF: 0.0512

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0124

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00329

Gnomad OTH AF: 0.0167

GnomAD2 exomes AF: 0.00690 AC: 1694 AN: 245568 AF XY: 0.00571

Gnomad AFR exome AF: 0.0518

Gnomad AMR exome AF: 0.00817

Gnomad ASJ exome AF: 0.00901

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000282

Gnomad NFE exome AF: 0.00367

Gnomad OTH exome AF: 0.0113

GnomAD4 exome AF: 0.00438 AC: 6402 AN: 1460730 Hom.: 57 Cov.: 31 AF XY: 0.00411 AC XY: 2987 AN XY: 726636

African (AFR) AF: 0.0530 AC: 1773 AN: 33456

American (AMR) AF: 0.00866 AC: 386 AN: 44584

Ashkenazi Jewish (ASJ) AF: 0.00835 AC: 218 AN: 26096

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

South Asian (SAS) AF: 0.000789 AC: 68 AN: 86146

European-Finnish (FIN) AF: 0.000375 AC: 20 AN: 53314

Middle Eastern (MID) AF: 0.0100 AC: 57 AN: 5692

European-Non Finnish (NFE) AF: 0.00306 AC: 3396 AN: 1111466

Other (OTH) AF: 0.00802 AC: 484 AN: 60318

GnomAD4 genome AF: 0.0172 AC: 2625 AN: 152376 Hom.: 57 Cov.: 33 AF XY: 0.0172 AC XY: 1280 AN XY: 74510

African (AFR) AF: 0.0513 AC: 2133 AN: 41586

American (AMR) AF: 0.0123 AC: 189 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0112 AC: 39 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00331 AC: 225 AN: 68040

Other (OTH) AF: 0.0166 AC: 35 AN: 2114

Alfa AF: 0.0107 Hom.: 23

Bravo AF: 0.0191

Asia WGS AF: 0.00520 AC: 18 AN: 3478

EpiCase AF: 0.00480

EpiControl AF: 0.00500

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 14, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.034
DANN	Benign	0.74
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;