Variant 12-27319396-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PP3_StrongBS2

The NM_015000.4(STK38L):c.1148T>C(p.Phe383Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,461,248 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000026 ( 1 hom. )

Consequence

STK38L
NM_015000.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.00

Variant links:

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]

STK38L links:

STK38L (HGNC:):

STK38L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.97

BS2

High AC in GnomAdExome4 at 38 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK38L	NM_015000.4 linkuse as main transcript	c.1148T>C	p.Phe383Ser	missense_variant	12/14	ENST00000389032.8	NP_055815.1	Q9Y2H1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
STK38L	ENST00000389032.8 linkuse as main transcript	c.1148T>C	p.Phe383Ser	missense_variant	12/14	1	NM_015000.4	ENSP00000373684.3	Q9Y2H1-1
STK38L	ENST00000536093.5 linkuse as main transcript	n.*379T>C		non_coding_transcript_exon_variant	6/8	2		ENSP00000443961.1	H0YGN4
STK38L	ENST00000543992.1 linkuse as main transcript	n.507T>C		non_coding_transcript_exon_variant	2/4	2
STK38L	ENST00000536093.5 linkuse as main transcript	n.*379T>C		3_prime_UTR_variant	6/8	2		ENSP00000443961.1	H0YGN4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000636

AC:

AN:

251382

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000523

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000260

AC:

AN:

1461248

Hom.:

Cov.:

AF XY:

0.0000399

AC XY:

AN XY:

726920

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000441

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000576

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2021

The c.1148T>C (p.F383S) alteration is located in exon 12 (coding exon 11) of the STK38L gene. This alteration results from a T to C substitution at nucleotide position 1148, causing the phenylalanine (F) at amino acid position 383 to be replaced by a serine (S). 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

0.97

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Pathogenic

0.33

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.41

Eigen

Pathogenic

0.94

Eigen_PC

Pathogenic

0.86

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

0.98

M_CAP

Uncertain

0.17

MetaRNN

Pathogenic

0.97

MetaSVM

Uncertain

0.47

MutationAssessor

Pathogenic

3.5

PrimateAI

Uncertain

0.77

PROVEAN

Pathogenic

-6.9

REVEL

Pathogenic

0.86

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.92

MutPred

0.91

Gain of disorder (P = 0.0049);

MVP

0.91

MPC

2.5

ClinPred

0.92

GERP RS

5.2

Varity_R

0.86

gMVP

0.98

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over