11-74001446-A-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_003356.4(UCP3):āc.905T>Gā(p.Met302Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_003356.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
UCP3 | NM_003356.4 | c.905T>G | p.Met302Arg | missense_variant | Exon 7 of 7 | ENST00000314032.9 | NP_003347.1 | |
UCP3 | XM_047427519.1 | c.905T>G | p.Met302Arg | missense_variant | Exon 6 of 6 | XP_047283475.1 | ||
UCP3 | XR_007062495.1 | n.3195T>G | non_coding_transcript_exon_variant | Exon 7 of 7 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251488Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135922
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461894Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 727248
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
This sequence change does not appear to have been previously described in patients with UCP3-related disorders and has been described in the gnomAD database in two heterozygous individuals which corresponds to a population frequency of 0.00080% (dbSNP rs757685199). The p.Met302Arg change affects a highly conserved amino acid residue located in a domain of the UCP3 protein that is known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Met302Arg substitution. Due to these contrasting evidences and the lack of functional studies, the clinical significance of the p.Met302Arg change remains unknown at this time. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at