1-36344125-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001282547.2(STK40):c.879T>C(p.Ile293=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0045 in 1,536,460 control chromosomes in the GnomAD database, including 237 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.023 (122 hom., cov: 30)
  • Exomes 𝑓: 0.0026 (115 hom.)
• Consequence: STK40 NM_001282547.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.29

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

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 1-36344125-A-G is Benign according to our data. Variant chr1-36344125-A-G is described in ClinVar as [Benign]. Clinvar id is 783934.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=3.29 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK40	NM_001282547.2	c.879T>C	p.Ile293=	synonymous_variant	8/11	ENST00000373132.4
STK40	NM_001282546.2	c.894T>C	p.Ile298=	synonymous_variant	8/11
STK40	NM_032017.3	c.879T>C	p.Ile293=	synonymous_variant	9/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK40	ENST00000373132.4	c.879T>C	p.Ile293=	synonymous_variant	8/11	1	NM_001282547.2	A1
STK40	ENST00000373130.7	c.894T>C	p.Ile298=	synonymous_variant	8/11	1		P4
STK40	ENST00000373129.7	c.879T>C	p.Ile293=	synonymous_variant	9/12	1		A1
STK40	ENST00000359297.6	c.879T>C	p.Ile293=	synonymous_variant	7/9	2

Frequencies

GnomAD3 genomes AF: 0.0231 AC: 3234 AN: 140166 Hom.: 123 Cov.: 30

Gnomad AFR AF: 0.0820

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00884

Gnomad ASJ AF: 0.00236

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00350

Gnomad NFE AF: 0.000440

Gnomad OTH AF: 0.0192

GnomAD3 exomes AF: 0.00600 AC: 1466 AN: 244168 Hom.: 38 AF XY: 0.00440 AC XY: 582 AN XY: 132168

Gnomad AFR exome AF: 0.0754

Gnomad AMR exome AF: 0.00377

Gnomad ASJ exome AF: 0.00244

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000167

Gnomad FIN exome AF: 0.0000474

Gnomad NFE exome AF: 0.000579

Gnomad OTH exome AF: 0.00525

GnomAD4 exome AF: 0.00263 AC: 3671 AN: 1396224 Hom.: 115 Cov.: 37 AF XY: 0.00228 AC XY: 1581 AN XY: 694766

Gnomad4 AFR exome AF: 0.0826

Gnomad4 AMR exome AF: 0.00521

Gnomad4 ASJ exome AF: 0.00190

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000201

Gnomad4 FIN exome AF: 0.0000210

Gnomad4 NFE exome AF: 0.000304

Gnomad4 OTH exome AF: 0.00697

GnomAD4 genome AF: 0.0232 AC: 3250 AN: 140236 Hom.: 122 Cov.: 30 AF XY: 0.0236 AC XY: 1590 AN XY: 67510

Gnomad4 AFR AF: 0.0822

Gnomad4 AMR AF: 0.00883

Gnomad4 ASJ AF: 0.00236

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000440

Gnomad4 OTH AF: 0.0191

Alfa AF: 0.0102 Hom.: 27

Bravo AF: 0.0250

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 14, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	7.9
Dann	Benign	0.74

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

LitVar

Other links and lift over

dbSNP: rs56317061; hg19: chr1-36809726;