rs35007621
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001384474.1(LOXHD1):āc.1742T>Cā(p.Val581Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00158 in 1,551,732 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001384474.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LOXHD1 | NM_001384474.1 | c.1742T>C | p.Val581Ala | missense_variant | 13/41 | ENST00000642948.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LOXHD1 | ENST00000642948.1 | c.1742T>C | p.Val581Ala | missense_variant | 13/41 | NM_001384474.1 | P1 | ||
LOXHD1 | ENST00000536736.5 | c.1742T>C | p.Val581Ala | missense_variant | 13/40 | 5 | |||
LOXHD1 | ENST00000441551.6 | c.1742T>C | p.Val581Ala | missense_variant | 13/39 | 5 | |||
LOXHD1 | ENST00000335730.6 | n.1055T>C | non_coding_transcript_exon_variant | 6/27 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00872 AC: 1326AN: 152146Hom.: 29 Cov.: 33
GnomAD3 exomes AF: 0.00158 AC: 250AN: 158692Hom.: 3 AF XY: 0.00117 AC XY: 98AN XY: 83540
GnomAD4 exome AF: 0.000805 AC: 1127AN: 1399468Hom.: 14 Cov.: 31 AF XY: 0.000677 AC XY: 467AN XY: 690242
GnomAD4 genome ? AF: 0.00874 AC: 1331AN: 152264Hom.: 30 Cov.: 33 AF XY: 0.00853 AC XY: 635AN XY: 74460
ClinVar
Submissions by phenotype
Autosomal recessive nonsyndromic hearing loss 77 Uncertain:1Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Counsyl | Mar 16, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 24, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 21, 2016 | p.Val581Ala in Exon 13 of LOXHD1: This variant is not expected to have clinical significance because it has been identified in 2.2% (61/2758) of African chromos omes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs35007621). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at