Variant 9-36643021-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_014791.4(MELK):c.859G>A(p.Val287Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000136 in 1,610,414 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00014 ( 1 hom. )

Consequence

MELK
NM_014791.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.30

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0070824623).

BP6

Variant 9-36643021-G-A is Benign according to our data. Variant chr9-36643021-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 728089.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MELK	NM_014791.4 linkuse as main transcript	c.859G>A	p.Val287Ile	missense_variant	11/18	ENST00000298048.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MELK	ENST00000298048.7 linkuse as main transcript	c.859G>A	p.Val287Ile	missense_variant	11/18	1	NM_014791.4	P1	Q14680-1

Frequencies

GnomAD3 genomes

AF:

0.000132

AC:

AN:

152042

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000786

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000945

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000517

AC:

128

AN:

247738

Hom.:

AF XY:

0.000388

AC XY:

AN XY:

133862

show subpopulations

Gnomad AFR exome

AF:

0.0000620

Gnomad AMR exome

AF:

0.00355

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000135

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00000888

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000136

AC:

199

AN:

1458372

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

725312

show subpopulations

Gnomad4 AFR exome

AF:

0.0000901

Gnomad4 AMR exome

AF:

0.00297

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000282

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.0000333

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000132

AC:

AN:

152042

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74256

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000786

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000945

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000219

ExAC

AF:

0.000461

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Apr 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.026

DANN

Benign

0.67

DEOGEN2

Benign

0.020

T;.;.;.;.;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.080

LIST_S2

Benign

0.77

T;T;T;T;T;T;T

M_CAP

Benign

0.0055

MetaRNN

Benign

0.0071

T;T;T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.2

L;.;.;L;.;.;.

MutationTaster

Benign

0.95

N;N;N;N;N;N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

0.16

N;N;N;N;N;N;N

REVEL

Benign

0.015

Sift

Benign

0.79

T;T;T;T;T;T;T

Sift4G

Benign

0.87

T;T;T;T;T;T;T

Polyphen

0.0

B;.;.;.;.;.;.

Vest4

0.15

MutPred

0.30

Gain of catalytic residue at V287 (P = 0.1031);.;.;Gain of catalytic residue at V287 (P = 0.1031);.;.;.;

MVP

0.19

MPC

0.087

ClinPred

0.0082

GERP RS

-3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.035

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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