9-36589541-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014791.4(MELK):c.150T>G(p.Asp50Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MELK NM_014791.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.817

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33311558).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MELK	NM_014791.4	c.150T>G	p.Asp50Glu	missense_variant	4/18	ENST00000298048.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MELK	ENST00000298048.7	c.150T>G	p.Asp50Glu	missense_variant	4/18	1	NM_014791.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Oct 22, 2021

The c.150T>G (p.D50E) alteration is located in exon 4 (coding exon 3) of the MELK gene. This alteration results from a T to G substitution at nucleotide position 150, causing the aspartic acid (D) at amino acid position 50 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	0.57
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
Cadd	Benign	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.11	T;.;.;.;T;.
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.94	D;T;D;D;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.33	T;T;T;T;T;T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	0.23	N;.;N;N;.;N
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-4.0	D;D;D;D;.;D
REVEL	Uncertain	0.34
Sift	Pathogenic	0.0	D;D;D;D;.;D
Sift4G	Pathogenic	0.0	D;D;D;D;T;D
Polyphen		1.0	D;.;.;.;.;.
Vest4		0.56
MutPred		0.41		Gain of disorder (P = 0.1153);.;Gain of disorder (P = 0.1153);Gain of disorder (P = 0.1153);Gain of disorder (P = 0.1153);Gain of disorder (P = 0.1153);
MVP		0.59
MPC		0.52
ClinPred		0.99	D
GERP RS		4.1
Varity_R		0.92
gMVP		0.66

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-36589538;