chr9-36599460-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_014791.4(MELK):c.541C>A(p.Gln181Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000112 in 1,612,000 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q181E) has been classified as Uncertain significance.
Frequency
Consequence
NM_014791.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MELK | NM_014791.4 | c.541C>A | p.Gln181Lys | missense_variant | 7/18 | ENST00000298048.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MELK | ENST00000298048.7 | c.541C>A | p.Gln181Lys | missense_variant | 7/18 | 1 | NM_014791.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152090Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251378Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135870
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1459910Hom.: 0 Cov.: 30 AF XY: 0.0000138 AC XY: 10AN XY: 726406
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152090Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74274
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 07, 2023 | The c.541C>A (p.Q181K) alteration is located in exon 7 (coding exon 6) of the MELK gene. This alteration results from a C to A substitution at nucleotide position 541, causing the glutamine (Q) at amino acid position 181 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at