12-27312632-T-G

Position:

• chr12-27312632-T-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_015000.4(STK38L):​c.477T>G​(p.Asp159Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: STK38L NM_015000.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.841

Genes affected

STK38L (HGNC:17848): (serine/threonine kinase 38 like) Enables ATP binding activity; magnesium ion binding activity; and protein serine/threonine kinase activity. Involved in intracellular signal transduction. Acts upstream of or within protein phosphorylation. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.946

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK38L	NM_015000.4	c.477T>G	p.Asp159Glu	missense_variant	6/14	ENST00000389032.8	NP_055815.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK38L	ENST00000389032.8	c.477T>G	p.Asp159Glu	missense_variant	6/14	1	NM_015000.4	ENSP00000373684.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461796 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727190

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2023

The c.477T>G (p.D159E) alteration is located in exon 6 (coding exon 5) of the STK38L gene. This alteration results from a T to G substitution at nucleotide position 477, causing the aspartic acid (D) at amino acid position 159 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Benign	0.0076	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T;T
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.065
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.077	D
MetaRNN	Pathogenic	0.95	D;D
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	1.6	L;.
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-3.5	D;D
REVEL	Uncertain	0.42
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.025	D;D
Polyphen		1.0	D;.
Vest4		0.63
MutPred		0.92		Loss of ubiquitination at K160 (P = 0.1453);.;
MVP		0.69
MPC		2.0
ClinPred		0.98	D
GERP RS		1.7
Varity_R		0.77
gMVP		0.67

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-27465565;