1-36344125-A-G

Variant names:

• chr1-36344125-A-G
• rs56317061
• NM_001282547.2:c.879T>C

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.879T>C​(p.Ile293Ile) 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.29
• Publications: 3 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=-0.59).
• 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
STK40	NM_001282547.2	c.879T>C	p.Ile293Ile	synonymous_variant	Exon 8 of 11	ENST00000373132.4	NP_001269476.1
STK40	NM_001282546.2	c.894T>C	p.Ile298Ile	synonymous_variant	Exon 8 of 11		NP_001269475.1
STK40	NM_032017.3	c.879T>C	p.Ile293Ile	synonymous_variant	Exon 9 of 12		NP_114406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK40	ENST00000373132.4	c.879T>C	p.Ile293Ile	synonymous_variant	Exon 8 of 11	1	NM_001282547.2	ENSP00000362224.4
STK40	ENST00000373130.7	c.894T>C	p.Ile298Ile	synonymous_variant	Exon 8 of 11	1		ENSP00000362222.3
STK40	ENST00000373129.7	c.879T>C	p.Ile293Ile	synonymous_variant	Exon 9 of 12	1		ENSP00000362221.3
STK40	ENST00000359297.6	c.879T>C	p.Ile293Ile	synonymous_variant	Exon 7 of 9	2		ENSP00000352245.2

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

GnomAD2 exomes AF: 0.00600 AC: 1466 AN: 244168 AF XY: 0.00440

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 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

African (AFR) AF: 0.0826 AC: 2637 AN: 31936

American (AMR) AF: 0.00521 AC: 218 AN: 41842

Ashkenazi Jewish (ASJ) AF: 0.00190 AC: 45 AN: 23664

East Asian (EAS) AF: 0.00 AC: 0 AN: 35200

South Asian (SAS) AF: 0.000201 AC: 17 AN: 84746

European-Finnish (FIN) AF: 0.0000210 AC: 1 AN: 47570

Middle Eastern (MID) AF: 0.00640 AC: 35 AN: 5468

European-Non Finnish (NFE) AF: 0.000304 AC: 325 AN: 1069424

Other (OTH) AF: 0.00697 AC: 393 AN: 56374

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

African (AFR) AF: 0.0822 AC: 3056 AN: 37182

American (AMR) AF: 0.00883 AC: 118 AN: 13362

Ashkenazi Jewish (ASJ) AF: 0.00236 AC: 8 AN: 3396

East Asian (EAS) AF: 0.00 AC: 0 AN: 4478

South Asian (SAS) AF: 0.00 AC: 0 AN: 4224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8580

Middle Eastern (MID) AF: 0.00379 AC: 1 AN: 264

European-Non Finnish (NFE) AF: 0.000440 AC: 29 AN: 65866

Other (OTH) AF: 0.0191 AC: 38 AN: 1988

Alfa AF: 0.0101 Hom.: 31

Bravo AF: 0.0250

Asia WGS AF: 0.00549 AC: 19 AN: 3478

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	-0.59
CADD	Benign	7.9
DANN	Benign	0.74
PhyloP100		3.3
Mutation Taster		=87/13	polymorphism (auto)

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: rs56317061; hg19: chr1-36809726;