rs200260213
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001384474.1(LOXHD1):c.3166G>A(p.Glu1056Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000825 in 1,551,880 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 (★). Synonymous variant affecting the same amino acid position (i.e. E1056E) has been classified as Likely benign.
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.3166G>A | p.Glu1056Lys | missense_variant | 20/41 | ENST00000642948.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LOXHD1 | ENST00000642948.1 | c.3166G>A | p.Glu1056Lys | missense_variant | 20/41 | NM_001384474.1 | P1 | ||
LOXHD1 | ENST00000536736.5 | c.3166G>A | p.Glu1056Lys | missense_variant | 20/40 | 5 | |||
LOXHD1 | ENST00000441551.6 | c.2599-2009G>A | intron_variant | 5 | |||||
LOXHD1 | ENST00000335730.6 | n.2479G>A | non_coding_transcript_exon_variant | 13/27 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000125 AC: 19AN: 152180Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000564 AC: 9AN: 159554Hom.: 0 AF XY: 0.0000477 AC XY: 4AN XY: 83878
GnomAD4 exome AF: 0.0000779 AC: 109AN: 1399700Hom.: 0 Cov.: 33 AF XY: 0.0000869 AC XY: 60AN XY: 690356
GnomAD4 genome ? AF: 0.000125 AC: 19AN: 152180Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74324
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 | Dec 15, 2017 | The p.Glu1056Lys variant in LOXHD1 has now been identified by our laboratory in 2 individuals with hearing loss, neither of whom had a second LOXHD1 variant. Th is variant has been identified in 6/73530 (0.008%) European chromosomes by the G enome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs20 0260213). Although this variant has been seen in the general population, its fre quency is not high enough to rule out a pathogenic role. Computational predictio n tools and conservation analysis suggest that the p.Glu1056Lys variant may impa ct the protein, though this information is not predictive enough to determine pa thogenicity. In summary, the clinical significance of the p.Glu1056Lys variant i s uncertain. ACMG/AMP Criteria applied: PP3. - |
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