chr7-87391639-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_021151.4(CROT):c.1352G>A(p.Arg451His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000023 in 1,610,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_021151.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CROT | NM_021151.4 | c.1352G>A | p.Arg451His | missense_variant | 14/18 | ENST00000331536.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CROT | ENST00000331536.8 | c.1352G>A | p.Arg451His | missense_variant | 14/18 | 1 | NM_021151.4 | P1 | |
CROT | ENST00000419147.6 | c.1436G>A | p.Arg479His | missense_variant | 15/19 | 2 | |||
CROT | ENST00000442291.1 | c.1352G>A | p.Arg451His | missense_variant | 13/17 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152100Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000445 AC: 11AN: 247368Hom.: 0 AF XY: 0.0000299 AC XY: 4AN XY: 133716
GnomAD4 exome AF: 0.0000219 AC: 32AN: 1458436Hom.: 0 Cov.: 31 AF XY: 0.0000179 AC XY: 13AN XY: 725422
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152100Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74266
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 23, 2021 | The c.1436G>A (p.R479H) alteration is located in exon 15 (coding exon 13) of the CROT gene. This alteration results from a G to A substitution at nucleotide position 1436, causing the arginine (R) at amino acid position 479 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