rs569341831
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001384474.1(LOXHD1):c.6268C>T(p.Arg2090Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000934 in 1,551,648 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. R2090Q) has been classified as Likely benign.
Frequency
Consequence
NM_001384474.1 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 |
---|---|---|---|---|---|---|---|
LOXHD1 | NM_001384474.1 | c.6268C>T | p.Arg2090Trp | missense_variant | 40/41 | ENST00000642948.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LOXHD1 | ENST00000642948.1 | c.6268C>T | p.Arg2090Trp | missense_variant | 40/41 | NM_001384474.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152074Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000211 AC: 33AN: 156760Hom.: 0 AF XY: 0.000289 AC XY: 24AN XY: 83034
GnomAD4 exome AF: 0.0000986 AC: 138AN: 1399456Hom.: 0 Cov.: 33 AF XY: 0.000141 AC XY: 97AN XY: 690232
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152192Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74390
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 | May 10, 2016 | Variant classified as Uncertain Significance - Favor Benign. The p.Arg2028Trp va riant in LOXHD1 has not been previously reported in individuals with hearing los s, but has been identified in 0.2% (14/7914) of South Asian chromosomes by the E xome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs56934 1831). The arginine (Arg) at position 2028 is not highly conserved in mammals an d evolutionary distant species, and 1 mammal (David's myotis bat) carries a tryp tophan (Trp) at this position, raising the possibility that this change at this position may be tolerated. Additional computational prediction tools do not prov ide strong support for or against an impact to the protein. In summary, while th e clinical significance of the p.Arg2028Trp variant is uncertain, these data sug gest that it is more likely to be benign. - |
Autosomal recessive nonsyndromic hearing loss 77 Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 17, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at