chr6-35805707-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_182548.4(LHFPL5):āc.37A>Gā(p.Ile13Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000014 ( 0 hom. )
Consequence
LHFPL5
NM_182548.4 missense
NM_182548.4 missense
Scores
1
9
7
Clinical Significance
Conservation
PhyloP100: 5.20
Genes affected
LHFPL5 (HGNC:21253): (LHFPL tetraspan subfamily member 5) This gene is a member of the lipoma HMGIC fusion partner (LHFP) gene family, which is a subset of the superfamily of tetraspan transmembrane protein encoding genes. Mutations in this gene result in deafness in humans, and a mutation in a similar gene in mice results in deafness and vestibular dysfunction with severe degeneration of the organ of Corti. It is proposed to function in hair bundle morphogenesis. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LHFPL5 | NM_182548.4 | c.37A>G | p.Ile13Val | missense_variant | 1/4 | ENST00000360215.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LHFPL5 | ENST00000360215.3 | c.37A>G | p.Ile13Val | missense_variant | 1/4 | 1 | NM_182548.4 | P1 | |
LHFPL5 | ENST00000651132.1 | c.37A>G | p.Ile13Val | missense_variant | 4/7 | P1 | |||
LHFPL5 | ENST00000651676.1 | c.37A>G | p.Ile13Val | missense_variant | 1/4 | P1 | |||
LHFPL5 | ENST00000651994.1 | c.37A>G | p.Ile13Val | missense_variant, NMD_transcript_variant | 1/4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251464Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135920
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461890Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727248
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GnomAD4 genome Cov.: 32
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32
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 13, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with LHFPL5-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.006%). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 13 of the LHFPL5 protein (p.Ile13Val). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;.
REVEL
Uncertain
Sift
Benign
T;.
Sift4G
Uncertain
D;.
Polyphen
P;P
Vest4
MutPred
Gain of methylation at K12 (P = 0.0499);Gain of methylation at K12 (P = 0.0499);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
Splicing
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at