18-46477511-C-T
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2
The NM_001384474.1(LOXHD1):c.6783G>A(p.Gly2261Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0005 in 1,550,738 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001384474.1 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LOXHD1 | NM_001384474.1 | c.6783G>A | p.Gly2261Gly | synonymous_variant | Exon 41 of 41 | ENST00000642948.1 | NP_001371403.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LOXHD1 | ENST00000642948.1 | c.6783G>A | p.Gly2261Gly | synonymous_variant | Exon 41 of 41 | NM_001384474.1 | ENSP00000496347.1 |
Frequencies
GnomAD3 genomes AF: 0.00263 AC: 400AN: 152214Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.000614 AC: 94AN: 153160Hom.: 1 AF XY: 0.000516 AC XY: 42AN XY: 81456
GnomAD4 exome AF: 0.000268 AC: 375AN: 1398406Hom.: 2 Cov.: 31 AF XY: 0.000213 AC XY: 147AN XY: 689738
GnomAD4 genome AF: 0.00263 AC: 401AN: 152332Hom.: 2 Cov.: 32 AF XY: 0.00262 AC XY: 195AN XY: 74490
ClinVar
Submissions by phenotype
not provided Benign:2
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Autosomal recessive nonsyndromic hearing loss 77 Uncertain:1
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. -
not specified Benign:1
p.Gly2199Gly in exon 40 of LOXHD1: This variant is not expected to have clinica l significance because it does not alter an amino acid residue and is not locate d within the splice consensus sequence. It has been identified in 1.7% (27/1596) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.b roadinstitute.org; dbSNP rs115835484). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at