rs181548456
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_001384474.1(LOXHD1):āc.6339T>Cā(p.Asn2113=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000284 in 1,550,450 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Consequence
NM_001384474.1 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LOXHD1 | NM_001384474.1 | c.6339T>C | p.Asn2113= | splice_region_variant, synonymous_variant | 40/41 | ENST00000642948.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LOXHD1 | ENST00000642948.1 | c.6339T>C | p.Asn2113= | splice_region_variant, synonymous_variant | 40/41 | NM_001384474.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000398 AC: 6AN: 150924Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000224 AC: 35AN: 156322Hom.: 0 AF XY: 0.000169 AC XY: 14AN XY: 82878
GnomAD4 exome AF: 0.0000272 AC: 38AN: 1399408Hom.: 0 Cov.: 30 AF XY: 0.0000275 AC XY: 19AN XY: 690210
GnomAD4 genome ? AF: 0.0000397 AC: 6AN: 151042Hom.: 0 Cov.: 32 AF XY: 0.0000678 AC XY: 5AN XY: 73748
ClinVar
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 06, 2012 | Asn2051Asn in exon 39 of LOXHD1: This variant has been identified in 0.04% (1/21 78) of chromosomes a broad population by the 1000 Genomes Project (dbSNP rs18154 8456). It is not expected to have clinical significance because it does not alte r an amino acid residue and is not located within the splice consensus sequence. - |
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Oct 23, 2023 | Variant summary: LOXHD1 c.6153T>C (p.Asn2051Asn) alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00022 in 156322 control chromosomes, predominantly at a frequency of 0.0032 within the East Asian subpopulation in the gnomAD database. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 2.86 fold of the estimated maximal expected allele frequency for a pathogenic variant in LOXHD1 causing Nonsyndromic Hearing Loss And Deafness, Type 77 phenotype (0.0011), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. To our knowledge, no occurrence of c.6153T>C in individuals affected with Nonsyndromic Hearing Loss And Deafness, Type 77 and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as benign. Based on the evidence outlined above, the variant was classified as likely benign. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at