9-36635412-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014791.4(MELK):c.834+2212T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,070 control chromosomes in the GnomAD database, including 1,884 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 0.14 (1884 hom., cov: 31)
• Consequence: MELK NM_014791.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MELK	NM_014791.4	c.834+2212T>G		intron_variant		ENST00000298048.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MELK	ENST00000298048.7	c.834+2212T>G		intron_variant		1	NM_014791.4	P1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21801 AN: 151950 Hom.: 1876 Cov.: 31

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0987

Gnomad ASJ AF: 0.0873

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.144 AC: 21843 AN: 152070 Hom.: 1884 Cov.: 31 AF XY: 0.145 AC XY: 10755 AN XY: 74358

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.0986

Gnomad4 ASJ AF: 0.0873

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.154

Alfa AF: 0.109 Hom.: 998

Bravo AF: 0.140

Asia WGS AF: 0.159 AC: 556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.6
Dann	Benign	0.37

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

Other links and lift over

dbSNP: rs2265346; hg19: chr9-36635409;