NM_001384474.1:c.2925_2933dupAGAGGAGGA
Variant summary
Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP3
The NM_001384474.1(LOXHD1):c.2925_2933dupAGAGGAGGA(p.Glu976_Glu978dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000129 in 1,551,784 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. E978E) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 7.1e-7 ( 0 hom. )
Consequence
LOXHD1
NM_001384474.1 disruptive_inframe_insertion
NM_001384474.1 disruptive_inframe_insertion
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 2.92
Publications
0 publications found
Genes affected
LOXHD1 (HGNC:26521): (lipoxygenase homology PLAT domains 1) This gene encodes a highly conserved protein consisting entirely of PLAT (polycystin/lipoxygenase/alpha-toxin) domains, thought to be involved in targeting proteins to the plasma membrane. Studies in mice show that this gene is expressed in the mechanosensory hair cells in the inner ear, and mutations in this gene lead to auditory defects, indicating that this gene is essential for normal hair cell function. Screening of human families segregating deafness identified a mutation in this gene which causes DFNB77, a progressive form of autosomal-recessive nonsyndromic hearing loss (ARNSHL). Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Mar 2010]
LOXHD1 Gene-Disease associations (from GenCC):
- autosomal recessive nonsyndromic hearing loss 77Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
- nonsyndromic genetic hearing lossInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- hearing loss, autosomal recessiveInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- Fuchs' endothelial dystrophyInheritance: AD Classification: LIMITED Submitted by: Illumina
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP3
Nonframeshift variant in repetitive region in NM_001384474.1
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001384474.1. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| LOXHD1 | NM_001384474.1 | MANE Select | c.2925_2933dupAGAGGAGGA | p.Glu976_Glu978dup | disruptive_inframe_insertion | Exon 19 of 41 | NP_001371403.1 | A0A2R8Y7K4 | |
| LOXHD1 | NM_144612.7 | c.2925_2933dupAGAGGAGGA | p.Glu976_Glu978dup | disruptive_inframe_insertion | Exon 19 of 40 | NP_653213.6 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| LOXHD1 | ENST00000642948.1 | MANE Select | c.2925_2933dupAGAGGAGGA | p.Glu976_Glu978dup | disruptive_inframe_insertion | Exon 19 of 41 | ENSP00000496347.1 | A0A2R8Y7K4 | |
| LOXHD1 | ENST00000536736.5 | TSL:5 | c.2925_2933dupAGAGGAGGA | p.Glu976_Glu978dup | disruptive_inframe_insertion | Exon 19 of 40 | ENSP00000444586.1 | F5GZB4 | |
| LOXHD1 | ENST00000441551.6 | TSL:5 | c.2599-2730_2599-2722dupAGAGGAGGA | intron | N/A | ENSP00000387621.2 | Q8IVV2-1 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152180Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152180
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 7.14e-7 AC: 1AN: 1399604Hom.: 0 Cov.: 37 AF XY: 0.00000145 AC XY: 1AN XY: 690300 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1399604
Hom.:
Cov.:
37
AF XY:
AC XY:
1
AN XY:
690300
show subpopulations
African (AFR)
AF:
AC:
1
AN:
31598
American (AMR)
AF:
AC:
0
AN:
35704
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25182
East Asian (EAS)
AF:
AC:
0
AN:
35740
South Asian (SAS)
AF:
AC:
0
AN:
79236
European-Finnish (FIN)
AF:
AC:
0
AN:
49360
Middle Eastern (MID)
AF:
AC:
0
AN:
5698
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1079034
Other (OTH)
AF:
AC:
0
AN:
58052
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000657 AC: 1AN: 152180Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74332 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152180
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74332
show subpopulations
African (AFR)
AF:
AC:
1
AN:
41464
American (AMR)
AF:
AC:
0
AN:
15290
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5176
South Asian (SAS)
AF:
AC:
0
AN:
4816
European-Finnish (FIN)
AF:
AC:
0
AN:
10622
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68018
Other (OTH)
AF:
AC:
0
AN:
2094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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