6-41033902-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_173561.3(UNC5CL):c.665G>A(p.Arg222His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,384 control chromosomes in the GnomAD database, with no homozygous occurrence. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_173561.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
UNC5CL | ENST00000244565.8 | c.665G>A | p.Arg222His | missense_variant | Exon 3 of 9 | 1 | NM_173561.3 | ENSP00000244565.3 | ||
UNC5CL | ENST00000373164.1 | c.665G>A | p.Arg222His | missense_variant | Exon 2 of 8 | 1 | ENSP00000362258.1 | |||
OARD1 | ENST00000482853.5 | n.*738G>A | non_coding_transcript_exon_variant | Exon 5 of 5 | 2 | ENSP00000420472.1 | ||||
OARD1 | ENST00000482853.5 | n.*738G>A | 3_prime_UTR_variant | Exon 5 of 5 | 2 | ENSP00000420472.1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152160Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 249028Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134948
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461224Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 726866
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152160Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74338
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.665G>A (p.R222H) alteration is located in exon 3 (coding exon 2) of the UNC5CL gene. This alteration results from a G to A substitution at nucleotide position 665, causing the arginine (R) at amino acid position 222 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