NM_003356.4:c.842T>C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_003356.4(UCP3):āc.842T>Cā(p.Leu281Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,614,024 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 (ā ā ).
Frequency
Consequence
NM_003356.4 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
UCP3 | NM_003356.4 | c.842T>C | p.Leu281Ser | missense_variant | Exon 7 of 7 | ENST00000314032.9 | NP_003347.1 | |
UCP3 | XM_047427519.1 | c.842T>C | p.Leu281Ser | missense_variant | Exon 6 of 6 | XP_047283475.1 | ||
UCP3 | XR_007062495.1 | n.3132T>C | non_coding_transcript_exon_variant | Exon 7 of 7 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152146Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251478Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135920
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461878Hom.: 0 Cov.: 30 AF XY: 0.00000825 AC XY: 6AN XY: 727240
GnomAD4 genome AF: 0.0000723 AC: 11AN: 152146Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74338
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.842T>C (p.L281S) alteration is located in exon 7 (coding exon 6) of the UCP3 gene. This alteration results from a T to C substitution at nucleotide position 842, causing the leucine (L) at amino acid position 281 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
UCP3-related disorder Uncertain:1
The UCP3 c.842T>C variant is predicted to result in the amino acid substitution p.Leu281Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.032% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
not provided Uncertain:1
This sequence change replaces leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 281 of the UCP3 protein (p.Leu281Ser). This variant is present in population databases (rs371947420, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with UCP3-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at