9-36652381-A-G

Variant names:

• chr9-36652381-A-G
• rs10973012
• NM_014791.4:c.1053+504A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014791.4(MELK):​c.1053+504A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.774 in 151,202 control chromosomes in the GnomAD database, including 47,718 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.77 (47718 hom., cov: 25)
• Consequence: MELK NM_014791.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.629
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MELK	NM_014791.4	c.1053+504A>G		intron_variant	Intron 12 of 17	ENST00000298048.7	NP_055606.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MELK	ENST00000298048.7	c.1053+504A>G		intron_variant	Intron 12 of 17	1	NM_014791.4	ENSP00000298048.2

Frequencies

GnomAD3 genomes AF: 0.775 AC: 117020 AN: 151084 Hom.: 47714 Cov.: 25

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.975

Gnomad AMR AF: 0.864

Gnomad ASJ AF: 0.870

Gnomad EAS AF: 0.891

Gnomad SAS AF: 0.804

Gnomad FIN AF: 0.856

Gnomad MID AF: 0.745

Gnomad NFE AF: 0.896

Gnomad OTH AF: 0.791

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.774 AC: 117054 AN: 151202 Hom.: 47718 Cov.: 25 AF XY: 0.775 AC XY: 57225 AN XY: 73846

African (AFR) AF: 0.488 AC: 20054 AN: 41104

American (AMR) AF: 0.864 AC: 13142 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.870 AC: 3021 AN: 3472

East Asian (EAS) AF: 0.892 AC: 4521 AN: 5070

South Asian (SAS) AF: 0.804 AC: 3811 AN: 4740

European-Finnish (FIN) AF: 0.856 AC: 8966 AN: 10474

Middle Eastern (MID) AF: 0.740 AC: 216 AN: 292

European-Non Finnish (NFE) AF: 0.896 AC: 60782 AN: 67834

Other (OTH) AF: 0.788 AC: 1654 AN: 2098

Alfa AF: 0.811 Hom.: 6350

Bravo AF: 0.765

Asia WGS AF: 0.820 AC: 2850 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.4
DANN	Benign	0.72
PhyloP100		0.63
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10973012; hg19: chr9-36652378;