8-96231854-T-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_006294.5(UQCRB):c.178A>T(p.Met60Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000421 in 1,614,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_006294.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UQCRB | NM_006294.5 | c.178A>T | p.Met60Leu | missense_variant | 3/4 | ENST00000287022.10 | |
UQCRB | NM_001254752.2 | c.178A>T | p.Met60Leu | missense_variant | 3/5 | ||
UQCRB | NM_001199975.3 | c.82A>T | p.Met28Leu | missense_variant | 4/5 | ||
UQCRB | NR_045639.2 | n.193A>T | non_coding_transcript_exon_variant | 3/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UQCRB | ENST00000287022.10 | c.178A>T | p.Met60Leu | missense_variant | 3/4 | 1 | NM_006294.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152212Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000231 AC: 58AN: 251406Hom.: 0 AF XY: 0.000206 AC XY: 28AN XY: 135870
GnomAD4 exome AF: 0.0000438 AC: 64AN: 1461830Hom.: 0 Cov.: 31 AF XY: 0.0000413 AC XY: 30AN XY: 727208
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152330Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74494
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 19, 2021 | The c.178A>T (p.M60L) alteration is located in exon 3 (coding exon 3) of the UQCRB gene. This alteration results from a A to T substitution at nucleotide position 178, causing the methionine (M) at amino acid position 60 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 11, 2022 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with UQCRB-related conditions. This variant is present in population databases (rs145974195, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces methionine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 60 of the UQCRB protein (p.Met60Leu). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at