rs727504727
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_031475.3(ESPN):c.439G>A(p.Ala147Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,612,788 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
ESPN
NM_031475.3 missense
NM_031475.3 missense
Scores
2
4
8
Clinical Significance
Conservation
PhyloP100: 9.58
Genes affected
ESPN (HGNC:13281): (espin) This gene encodes a multifunctional actin-bundling protein. It plays a major role in regulating the organization, dimensions, dynamics, and signaling capacities of the actin filament-rich, microvillus-type specializations that mediate sensory transduction in various mechanosensory and chemosensory cells. Mutations in this gene are associated with autosomal recessive neurosensory deafness, and autosomal dominant sensorineural deafness without vestibular involvement. [provided by RefSeq, Nov 2009]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ESPN | NM_031475.3 | c.439G>A | p.Ala147Thr | missense_variant | 2/13 | ENST00000645284.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ESPN | ENST00000645284.1 | c.439G>A | p.Ala147Thr | missense_variant | 2/13 | NM_031475.3 | P1 | ||
ESPN | ENST00000636330.1 | c.439G>A | p.Ala147Thr | missense_variant | 2/11 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152104Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249302Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135098
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GnomAD4 exome AF: 0.00000616 AC: 9AN: 1460684Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 726568
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152104Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74284
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Sep 03, 2013 | The Ala147Thr variant in ESPN has not been reported in individuals with hearing loss or in large population studies. Computational analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide st rong support for or against an impact to the protein. In summary, additional inf ormation is needed to fully assess the clinical significance of the Ala147Thr va riant. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
Polyphen
D;.;D
Vest4
0.58
MutPred
Gain of phosphorylation at A147 (P = 0.0792);Gain of phosphorylation at A147 (P = 0.0792);Gain of phosphorylation at A147 (P = 0.0792);
MVP
0.67
MPC
0.63
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at