NM_001384474.1:c.4756C>T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001384474.1(LOXHD1):c.4756C>T(p.Arg1586Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000702 in 1,551,676 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001384474.1 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 |
---|---|---|---|---|---|---|---|---|
LOXHD1 | NM_001384474.1 | c.4756C>T | p.Arg1586Cys | missense_variant | Exon 31 of 41 | ENST00000642948.1 | NP_001371403.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LOXHD1 | ENST00000642948.1 | c.4756C>T | p.Arg1586Cys | missense_variant | Exon 31 of 41 | NM_001384474.1 | ENSP00000496347.1 |
Frequencies
GnomAD3 genomes AF: 0.0000986 AC: 15AN: 152154Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000763 AC: 12AN: 157302Hom.: 0 AF XY: 0.0000723 AC XY: 6AN XY: 82934
GnomAD4 exome AF: 0.0000672 AC: 94AN: 1399404Hom.: 0 Cov.: 32 AF XY: 0.0000782 AC XY: 54AN XY: 690210
GnomAD4 genome AF: 0.0000985 AC: 15AN: 152272Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11AN XY: 74442
ClinVar
Submissions by phenotype
Autosomal recessive nonsyndromic hearing loss 77 Uncertain:2
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not specified Uncertain:1
The p.Arg1586Cys variant in LOXHD1 has not been previously reported in individua ls with hearing loss or in large population studies. Computational prediction to ols and conservation analysis suggest that the p.Arg1586Cys variant may impact t he protein, though this information is not predictive enough to determine pathog enicity. In summary, the clinical significance of the p.Arg1586Cys variant is un certain. -
Inborn genetic diseases Uncertain:1
The c.4756C>T (p.R1586C) alteration is located in exon 31 (coding exon 31) of the LOXHD1 gene. This alteration results from a C to T substitution at nucleotide position 4756, causing the arginine (R) at amino acid position 1586 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1586 of the LOXHD1 protein (p.Arg1586Cys). This variant is present in population databases (rs773223976, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with LOXHD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 505399). 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: "Deleterious"; PolyPhen-2: "Probably 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