18-46524586-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001384474.1(LOXHD1):ā€‹c.4756C>Gā€‹(p.Arg1586Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000715 in 1,399,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 7.1e-7 ( 0 hom. )

Consequence

LOXHD1
NM_001384474.1 missense

Scores

1
10
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.67
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.34317493).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LOXHD1NM_001384474.1 linkc.4756C>G p.Arg1586Gly missense_variant Exon 31 of 41 ENST00000642948.1 NP_001371403.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LOXHD1ENST00000642948.1 linkc.4756C>G p.Arg1586Gly missense_variant Exon 31 of 41 NM_001384474.1 ENSP00000496347.1 A0A2R8Y7K4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000636
AC:
1
AN:
157302
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
82934
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000165
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
7.15e-7
AC:
1
AN:
1399404
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
690210
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.27e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.92
BayesDel_addAF
Uncertain
0.045
T
BayesDel_noAF
Benign
-0.16
CADD
Pathogenic
26
DANN
Uncertain
0.98
DEOGEN2
Benign
0.063
.;.;T;.;.;T
Eigen
Uncertain
0.48
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Uncertain
0.91
D;D;D;D;D;D
M_CAP
Benign
0.024
T
MetaRNN
Benign
0.34
T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
PrimateAI
Uncertain
0.66
T
PROVEAN
Uncertain
-3.2
.;D;.;D;.;.
REVEL
Benign
0.19
Sift
Uncertain
0.016
.;D;.;D;.;.
Sift4G
Uncertain
0.010
D;T;T;D;.;D
Polyphen
0.99
.;.;.;D;.;.
Vest4
0.38
MutPred
0.30
.;.;.;Loss of solvent accessibility (P = 0.0769);Loss of solvent accessibility (P = 0.0769);.;
MVP
0.30
ClinPred
0.95
D
GERP RS
5.1
Varity_R
0.80
gMVP
0.50

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs773223976; hg19: chr18-44104549; API