rs61733519
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001384474.1(LOXHD1):c.5802C>A(p.Asn1934Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00399 in 1,551,990 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LOXHD1 | NM_001384474.1 | c.5802C>A | p.Asn1934Lys | missense_variant | Exon 37 of 41 | ENST00000642948.1 | NP_001371403.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LOXHD1 | ENST00000642948.1 | c.5802C>A | p.Asn1934Lys | missense_variant | Exon 37 of 41 | NM_001384474.1 | ENSP00000496347.1 |
Frequencies
GnomAD3 genomes AF: 0.00308 AC: 469AN: 152198Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.00278 AC: 439AN: 157646Hom.: 1 AF XY: 0.00244 AC XY: 203AN XY: 83288
GnomAD4 exome AF: 0.00409 AC: 5718AN: 1399674Hom.: 12 Cov.: 31 AF XY: 0.00385 AC XY: 2659AN XY: 690322
GnomAD4 genome AF: 0.00308 AC: 469AN: 152316Hom.: 1 Cov.: 32 AF XY: 0.00287 AC XY: 214AN XY: 74486
ClinVar
Submissions by phenotype
Autosomal recessive nonsyndromic hearing loss 77 Uncertain:2Benign:2
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This test identified a heterozygous variant (c.5616C>A;p.Asn1872Lys) in the LOXHD1 gene. This gene has been associated with an autosomal recessive form of hearing loss (DFNB77; MIM: 613079). This variant is considered a variant of unknown significance, as it has not been reported in literature; however, it was seen in 0.2% of individuals in ExAC. -
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
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not provided Uncertain:1Benign:3
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LOXHD1: BP4, BS2 -
Inborn genetic diseases Uncertain:1
The c.5616C>A (p.N1872K) alteration is located in exon 36 (coding exon 36) of the LOXHD1 gene. This alteration results from a C to A substitution at nucleotide position 5616, causing the asparagine (N) at amino acid position 1872 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not specified Benign:1
p.Asn1872Lys in exon 36 of LOXHD1: This variant is not expected to have clinical significance because it has been identified in 0.4% (309/73462) of European chr omosomes, including 1 homozygous individual, by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs61733519). -
LOXHD1-related disorder Benign:1
This variant is classified as likely 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