Variant 9-36589580-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014791.4(MELK):c.189C>G(p.Asn63Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Consequence

MELK
NM_014791.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.214

Variant links:

Genes affected

MELK (HGNC:16870): (maternal embryonic leucine zipper kinase) Enables calcium ion binding activity; non-membrane spanning protein tyrosine kinase activity; and protein serine/threonine kinase activity. Involved in apoptotic process; cell population proliferation; and protein autophosphorylation. Located in cell cortex and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

MELK links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17860892).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MELK	NM_014791.4 linkuse as main transcript	c.189C>G	p.Asn63Lys	missense_variant	4/18	ENST00000298048.7	NP_055606.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MELK	ENST00000298048.7 linkuse as main transcript	c.189C>G	p.Asn63Lys	missense_variant	4/18	1	NM_014791.4	ENSP00000298048	P1	Q14680-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152116

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

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

Mar 02, 2023

The c.189C>G (p.N63K) alteration is located in exon 4 (coding exon 3) of the MELK gene. This alteration results from a C to G substitution at nucleotide position 189, causing the asparagine (N) at amino acid position 63 to be replaced by a lysine (K). 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

Benign

0.18

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.099

T;.;.;.;T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.86

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.93

D;D;D;D;D;D

M_CAP

Benign

0.075

MetaRNN

Benign

0.18

T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.80

N;.;N;N;.;N

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;N

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-3.4

D;D;D;D;.;D

REVEL

Benign

0.14

Sift

Uncertain

0.011

D;D;D;D;.;T

Sift4G

Benign

0.12

T;T;T;T;T;D

Polyphen

0.15

B;.;.;.;.;.

Vest4

0.67

MutPred

0.41

Gain of disorder (P = 0.0655);.;Gain of disorder (P = 0.0655);Gain of disorder (P = 0.0655);Gain of disorder (P = 0.0655);Gain of disorder (P = 0.0655);

MVP

0.44

MPC

0.36

ClinPred

0.97

GERP RS

-0.39

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.64

gMVP

0.47

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