chr11-10751456-A-G
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_ModeratePP5_Moderate
The NM_014633.5(CTR9):c.44A>G(p.Glu15Gly) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 13/23 in silico tools predict a damaging outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Consequence
NM_014633.5 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CTR9 | NM_014633.5 | c.44A>G | p.Glu15Gly | missense_variant, splice_region_variant | Exon 1 of 25 | ENST00000361367.7 | NP_055448.1 | |
CTR9 | NM_001346279.2 | c.44A>G | p.Glu15Gly | missense_variant, splice_region_variant | Exon 1 of 24 | NP_001333208.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CTR9 | ENST00000361367.7 | c.44A>G | p.Glu15Gly | missense_variant, splice_region_variant | Exon 1 of 25 | 1 | NM_014633.5 | ENSP00000355013.2 | ||
CTR9 | ENST00000524523.1 | c.5A>G | p.Glu2Gly | missense_variant, splice_region_variant | Exon 1 of 8 | 5 | ENSP00000431458.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
The c.44A>G (p.E15G) alteration is located in exon 1 (coding exon 1) of the CTR9 gene. This alteration results from an A to G substitution at nucleotide position 44, causing the glutamic acid (E) at amino acid position 15 to be replaced by a glycine (G). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Two other alterations at the same codon, c.43G>A (p.E15K) and c.45G>C (p.E15D), have been determined to be the result of a de novo mutation in individuals with features consistent with CTR9-related neurodevelopmental disorder (Meuwissen, 2022; Suzuki, 2022). This amino acid position is highly conserved in available vertebrate species. This missense alteration is located in a region that has a low rate of benign missense variation (Lek, 2016; Firth, 2009). This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as likely pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.