6-106629697-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4BS1_Supporting
The NM_018292.5(QRSL1):c.16C>T(p.Leu6Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000504 in 1,606,450 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_018292.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
QRSL1 | ENST00000369046.8 | c.16C>T | p.Leu6Phe | missense_variant | Exon 1 of 11 | 1 | NM_018292.5 | ENSP00000358042.4 | ||
QRSL1 | ENST00000369044.1 | c.16C>T | p.Leu6Phe | missense_variant | Exon 1 of 7 | 2 | ENSP00000358040.1 | |||
QRSL1 | ENST00000467262.1 | n.99C>T | non_coding_transcript_exon_variant | Exon 1 of 4 | 3 | |||||
RTN4IP1 | ENST00000369063.8 | c.-676G>A | upstream_gene_variant | 1 | NM_032730.5 | ENSP00000358059.3 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152160Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000257 AC: 6AN: 233134Hom.: 0 AF XY: 0.0000237 AC XY: 3AN XY: 126326
GnomAD4 exome AF: 0.0000488 AC: 71AN: 1454290Hom.: 0 Cov.: 32 AF XY: 0.0000526 AC XY: 38AN XY: 722526
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152160Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74328
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.16C>T (p.L6F) alteration is located in exon 1 (coding exon 1) of the QRSL1 gene. This alteration results from a C to T substitution at nucleotide position 16, causing the leucine (L) at amino acid position 6 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Combined oxidative phosphorylation deficiency 40 Uncertain:1
A heterozygous missense variant was identified, NM_018292.4(QRSL1):c.16C>T in exon 1 of 11 of the QRSL1 gene. This substitution is predicted to create a minor amino acid change from leucine to phenylalanine at position 6 of the protein, NP_060762.3(QRSL1):p.(Leu6Phe). The leucine at this position has very high conservation (100 vertebrates, UCSC), and is located within the Amidase superfamily domain. In silico software predictions of the pathogenicity of this variant are conflicting (Polyphen, SIFT, CADD, Mutation Taster). The variant is present in the gnomAD population database at a frequency of 0.003% (8 heterozygotes, 0 homozygotes). This variant has not been previously reported in clinical cases. Based on information available at the time of curation, this variant has been classified as a VARIANT of UNCERTAIN SIGNIFICANCE (VUS). -
not provided Uncertain:1
This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 6 of the QRSL1 protein (p.Leu6Phe). This variant is present in population databases (rs373031772, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with QRSL1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1460859). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt QRSL1 protein function with a negative predictive value of 80%. 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