rs779218726
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_001384474.1(LOXHD1):c.6084C>T(p.Gly2028=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000071 in 1,549,088 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.000067 ( 0 hom., cov: 30)
Exomes 𝑓: 0.000071 ( 0 hom. )
Consequence
LOXHD1
NM_001384474.1 synonymous
NM_001384474.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.626
Genes affected
LOXHD1 (HGNC:26521): (lipoxygenase homology PLAT domains 1) This gene encodes a highly conserved protein consisting entirely of PLAT (polycystin/lipoxygenase/alpha-toxin) domains, thought to be involved in targeting proteins to the plasma membrane. Studies in mice show that this gene is expressed in the mechanosensory hair cells in the inner ear, and mutations in this gene lead to auditory defects, indicating that this gene is essential for normal hair cell function. Screening of human families segregating deafness identified a mutation in this gene which causes DFNB77, a progressive form of autosomal-recessive nonsyndromic hearing loss (ARNSHL). Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Mar 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
?
Variant 18-46485117-G-A is Benign according to our data. Variant chr18-46485117-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 517332.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.626 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LOXHD1 | NM_001384474.1 | c.6084C>T | p.Gly2028= | synonymous_variant | 39/41 | ENST00000642948.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LOXHD1 | ENST00000642948.1 | c.6084C>T | p.Gly2028= | synonymous_variant | 39/41 | NM_001384474.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000668 AC: 10AN: 149608Hom.: 0 Cov.: 30
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GnomAD3 exomes AF: 0.0000822 AC: 13AN: 158176Hom.: 0 AF XY: 0.0000838 AC XY: 7AN XY: 83494
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GnomAD4 exome AF: 0.0000715 AC: 100AN: 1399364Hom.: 0 Cov.: 35 AF XY: 0.0000652 AC XY: 45AN XY: 690202
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GnomAD4 genome ? AF: 0.0000668 AC: 10AN: 149724Hom.: 0 Cov.: 30 AF XY: 0.0000686 AC XY: 5AN XY: 72896
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 20, 2017 | p.Gly1966Gly in exon 38 of LOXHD1: This variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located within the splice consensus sequence. This variant has been identified in 1/927 0 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.br oadinstitute.org; dbSNP rs779218726). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at