rs369890906
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001384474.1(LOXHD1):c.4757G>T(p.Arg1586Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000122 in 1,551,596 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1586C) has been classified 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 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LOXHD1 | NM_001384474.1 | c.4757G>T | p.Arg1586Leu | missense_variant | 31/41 | ENST00000642948.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LOXHD1 | ENST00000642948.1 | c.4757G>T | p.Arg1586Leu | missense_variant | 31/41 | NM_001384474.1 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152196Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000127 AC: 2AN: 157336Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 82940
GnomAD4 exome AF: 0.0000114 AC: 16AN: 1399400Hom.: 0 Cov.: 32 AF XY: 0.0000130 AC XY: 9AN XY: 690204
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152196Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74340
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 02, 2015 | The p.Arg1586Leu variant in LOXHD1 has not been previously reported in individua ls with hearing loss. This variant has been identified in 1/2864 of African chro mosomes and in 1/9204 of European chromosomes by the Exome Aggregation Consortiu m (ExAC, http://exac.broadinstitute.org; dbSNP rs369890906); though this frequen cy is not high enough to rule out pathogenicity. Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Arg1586Leu varia nt is uncertain. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 30, 2021 | The c.4757G>T (p.R1586L) alteration is located in exon 31 (coding exon 31) of the LOXHD1 gene. This alteration results from a G to T substitution at nucleotide position 4757, causing the arginine (R) at amino acid position 1586 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Autosomal recessive nonsyndromic hearing loss 77 Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at