chr17-80994651-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_024591.5(CHMP6):c.134G>A(p.Arg45His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,584,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R45C) has been classified as Uncertain significance.
Frequency
Consequence
NM_024591.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHMP6 | NM_024591.5 | c.134G>A | p.Arg45His | missense_variant | 2/8 | ENST00000325167.9 | |
CHMP6 | XM_005257668.1 | c.134G>A | p.Arg45His | missense_variant | 2/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHMP6 | ENST00000325167.9 | c.134G>A | p.Arg45His | missense_variant | 2/8 | 1 | NM_024591.5 | P1 | |
CHMP6 | ENST00000572778.5 | c.71G>A | p.Arg24His | missense_variant | 1/6 | 2 | |||
CHMP6 | ENST00000571457.1 | c.8G>A | p.Arg3His | missense_variant | 1/7 | 3 | |||
CHMP6 | ENST00000572525.5 | c.-125G>A | 5_prime_UTR_variant | 2/8 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000118 AC: 18AN: 152158Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000681 AC: 13AN: 190976Hom.: 0 AF XY: 0.0000965 AC XY: 10AN XY: 103624
GnomAD4 exome AF: 0.000106 AC: 152AN: 1431774Hom.: 0 Cov.: 31 AF XY: 0.000116 AC XY: 82AN XY: 709360
GnomAD4 genome ? AF: 0.000118 AC: 18AN: 152276Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6AN XY: 74470
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 13, 2021 | The c.134G>A (p.R45H) alteration is located in exon 2 (coding exon 2) of the CHMP6 gene. This alteration results from a G to A substitution at nucleotide position 134, causing the arginine (R) at amino acid position 45 to be replaced by a histidine (H). 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