rs140042576
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_001384474.1(LOXHD1):c.4822G>A(p.Val1608Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000369 in 1,551,754 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. V1608V) has been classified as Likely benign.
Frequency
Consequence
NM_001384474.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LOXHD1 | NM_001384474.1 | c.4822G>A | p.Val1608Ile | missense_variant | 31/41 | ENST00000642948.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LOXHD1 | ENST00000642948.1 | c.4822G>A | p.Val1608Ile | missense_variant | 31/41 | NM_001384474.1 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00196 AC: 299AN: 152222Hom.: 1 Cov.: 33
GnomAD3 exomes AF: 0.000588 AC: 93AN: 158170Hom.: 0 AF XY: 0.000420 AC XY: 35AN XY: 83338
GnomAD4 exome AF: 0.000192 AC: 268AN: 1399414Hom.: 0 Cov.: 32 AF XY: 0.000185 AC XY: 128AN XY: 690216
GnomAD4 genome AF: 0.00200 AC: 305AN: 152340Hom.: 1 Cov.: 33 AF XY: 0.00181 AC XY: 135AN XY: 74494
ClinVar
Submissions by phenotype
Autosomal recessive nonsyndromic hearing loss 77 Uncertain:1Benign:1
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 11, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Nov 01, 2017 | - - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 26, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 03, 2015 | p.Val1608Ile in exon 31 of LOXHD1: This variant is not expected to have clinical significance because it has been identified in 0.8% (22/2752) of African chromo somes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs140042576). In addition, the valine (Val) at position 1608 is not cons erved across species, with several mammals having an isoleucine (Ile) at this po sition. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2024 | - - |
LOXHD1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 03, 2021 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at