Variant 9-36583645-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_014791.4(MELK):c.77A>G(p.Lys26Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0059 in 1,611,680 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K26T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0051 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0060 ( 47 hom. )

Consequence

MELK
NM_014791.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 8.34

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010416746).

BP6

Variant 9-36583645-A-G is Benign according to our data. Variant chr9-36583645-A-G is described in ClinVar as [Benign]. Clinvar id is 779255.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MELK	NM_014791.4 linkuse as main transcript	c.77A>G	p.Lys26Arg	missense_variant	3/18	ENST00000298048.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MELK	ENST00000298048.7 linkuse as main transcript	c.77A>G	p.Lys26Arg	missense_variant	3/18	1	NM_014791.4	P1	Q14680-1

Frequencies

GnomAD3 genomes

AF:

0.00511

AC:

777

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000990

Gnomad AMI

AF:

0.0451

Gnomad AMR

AF:

0.00367

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.0104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00728

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00509

AC:

1279

AN:

251116

Hom.:

AF XY:

0.00511

AC XY:

693

AN XY:

135748

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.00249

Gnomad ASJ exome

AF:

0.00585

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.0116

Gnomad NFE exome

AF:

0.00723

Gnomad OTH exome

AF:

0.00587

GnomAD4 exome

AF:

0.00598

AC:

8727

AN:

1459450

Hom.:

Cov.:

AF XY:

0.00594

AC XY:

4313

AN XY:

726048

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.00275

Gnomad4 ASJ exome

AF:

0.00518

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.000175

Gnomad4 FIN exome

AF:

0.0118

Gnomad4 NFE exome

AF:

0.00676

Gnomad4 OTH exome

AF:

0.00466

GnomAD4 genome

AF:

0.00510

AC:

777

AN:

152230

Hom.:

Cov.:

AF XY:

0.00500

AC XY:

372

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.000987

Gnomad4 AMR

AF:

0.00367

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.0104

Gnomad4 NFE

AF:

0.00728

Gnomad4 OTH

AF:

0.00711

Alfa

AF:

0.00665

Hom.:

Bravo

AF:

0.00471

TwinsUK

AF:

0.00728

AC:

ALSPAC

AF:

0.00675

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00767

AC:

ExAC

AF:

0.00492

AC:

597

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 08, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Uncertain

-0.080

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.11

T;.;.;T;.

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

D;D;D;D;D

MetaRNN

Benign

0.010

T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.070

N;N;N;.;N

MutationTaster

Benign

1.0

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

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-2.7

D;D;D;.;D

REVEL

Uncertain

0.43

Sift

Pathogenic

0.0

D;D;D;.;D

Sift4G

Benign

0.14

T;T;T;T;T

Polyphen

1.0

D;.;.;.;.

Vest4

0.80

MVP

0.51

MPC

0.49

ClinPred

0.019

GERP RS

5.3

Varity_R

0.94

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

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