9-36589639-T-A

Position:

• chr9-36589639-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014791.4(MELK):​c.248T>A​(p.Phe83Tyr) variant causes a missense change. 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: 5.62

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21548203).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MELK	NM_014791.4	c.248T>A	p.Phe83Tyr	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	c.248T>A	p.Phe83Tyr	missense_variant	4/18	1	NM_014791.4	ENSP00000298048	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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

Jun 03, 2024

The c.248T>A (p.F83Y) alteration is located in exon 4 (coding exon 3) of the MELK gene. This alteration results from a T to A substitution at nucleotide position 248, causing the phenylalanine (F) at amino acid position 83 to be replaced by a tyrosine (Y). 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	0.22
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.041	T;.;.;.;T;.
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.025
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D;D;D;D;D;D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.22	T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.77	N;.;N;N;.;N
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;N
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-2.0	N;N;N;N;.;N
REVEL	Benign	0.17
Sift	Benign	0.12	T;T;T;T;.;T
Sift4G	Benign	0.16	T;T;T;T;T;T
Polyphen		0.53	P;.;.;.;.;.
Vest4		0.66
MutPred		0.60		Loss of methylation at K81 (P = 0.0781);.;Loss of methylation at K81 (P = 0.0781);Loss of methylation at K81 (P = 0.0781);Loss of methylation at K81 (P = 0.0781);Loss of methylation at K81 (P = 0.0781);
MVP		0.14
MPC		0.17
ClinPred		0.85	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.50
gMVP		0.57

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-36589636;