rs376334860
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7
The NM_001384474.1(LOXHD1):c.3561G>A(p.Lys1187=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000547 in 1,551,940 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 0.00022 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00058 ( 0 hom. )
Consequence
LOXHD1
NM_001384474.1 synonymous
NM_001384474.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.645
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 Benign. Variant got -9 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.23).
BP6
?
Variant 18-46545375-C-T is Benign according to our data. Variant chr18-46545375-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 227518.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.645 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LOXHD1 | NM_001384474.1 | c.3561G>A | p.Lys1187= | synonymous_variant | 23/41 | ENST00000642948.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LOXHD1 | ENST00000642948.1 | c.3561G>A | p.Lys1187= | synonymous_variant | 23/41 | NM_001384474.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000224 AC: 34AN: 152104Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000262 AC: 42AN: 160390Hom.: 0 AF XY: 0.000250 AC XY: 21AN XY: 84076
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GnomAD4 exome AF: 0.000582 AC: 815AN: 1399836Hom.: 0 Cov.: 30 AF XY: 0.000540 AC XY: 373AN XY: 690394
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GnomAD4 genome ? AF: 0.000224 AC: 34AN: 152104Hom.: 0 Cov.: 31 AF XY: 0.000229 AC XY: 17AN XY: 74298
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
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 22, 2015 | p.Lys1187Lys in Exon 23 of LOXHD1: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wi thin the splice consensus sequence, and has been identified in 4/9450 European c hromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute .org; dbSNP rs376334860). - |
Autosomal recessive nonsyndromic hearing loss 77 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Counsyl | Jan 30, 2018 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
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