X-70277476-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_004312.3(ARR3):c.556C>T(p.Arg186Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000471 in 1,209,803 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 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. R186H) has been classified as Uncertain significance.
Frequency
Consequence
NM_004312.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARR3 | NM_004312.3 | c.556C>T | p.Arg186Cys | missense_variant | 9/17 | ENST00000307959.9 | |
ARR3 | XM_047442105.1 | c.580C>T | p.Arg194Cys | missense_variant | 8/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARR3 | ENST00000307959.9 | c.556C>T | p.Arg186Cys | missense_variant | 9/17 | 1 | NM_004312.3 | P1 | |
ARR3 | ENST00000374495.7 | c.556C>T | p.Arg186Cys | missense_variant | 9/16 | 1 |
Frequencies
GnomAD3 genomes AF: 0.000143 AC: 16AN: 112086Hom.: 0 Cov.: 24 AF XY: 0.0000876 AC XY: 3AN XY: 34242
GnomAD3 exomes AF: 0.0000607 AC: 11AN: 181262Hom.: 0 AF XY: 0.0000152 AC XY: 1AN XY: 65872
GnomAD4 exome AF: 0.0000374 AC: 41AN: 1097717Hom.: 0 Cov.: 32 AF XY: 0.0000193 AC XY: 7AN XY: 363089
GnomAD4 genome AF: 0.000143 AC: 16AN: 112086Hom.: 0 Cov.: 24 AF XY: 0.0000876 AC XY: 3AN XY: 34242
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 13, 2023 | The c.556C>T (p.R186C) alteration is located in exon 9 (coding exon 8) of the ARR3 gene. This alteration results from a C to T substitution at nucleotide position 556, causing the arginine (R) at amino acid position 186 to be replaced by a cysteine (C). 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