rs201576880
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_001384474.1(LOXHD1):āc.3449A>Gā(p.Gln1150Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000209 in 1,551,742 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Q1150Q) has been classified as Likely benign.
Frequency
Consequence
NM_001384474.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LOXHD1 | NM_001384474.1 | c.3449A>G | p.Gln1150Arg | missense_variant | 22/41 | ENST00000642948.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LOXHD1 | ENST00000642948.1 | c.3449A>G | p.Gln1150Arg | missense_variant | 22/41 | NM_001384474.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000834 AC: 127AN: 152230Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000221 AC: 35AN: 158338Hom.: 0 AF XY: 0.000144 AC XY: 12AN XY: 83414
GnomAD4 exome AF: 0.000141 AC: 198AN: 1399394Hom.: 0 Cov.: 34 AF XY: 0.000136 AC XY: 94AN XY: 690204
GnomAD4 genome ? AF: 0.000827 AC: 126AN: 152348Hom.: 0 Cov.: 33 AF XY: 0.000859 AC XY: 64AN XY: 74504
ClinVar
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2022 | LOXHD1: BP4, BS1:Supporting - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 14, 2023 | The c.3449A>G (p.Q1150R) alteration is located in exon 22 (coding exon 22) of the LOXHD1 gene. This alteration results from a A to G substitution at nucleotide position 3449, causing the glutamine (Q) at amino acid position 1150 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 04, 2016 | p.Gln1150Arg in exon 22 of LOXHD1: This variant is not expected to have clinical significance because it has been identified in 0.36% (10/2758) of African chrom osomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org ; dbSNP rs201576880). In addition, computational tools and conservation analysis does not suggest an impact to the protein. - |
LOXHD1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 04, 2023 | 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