rs373242735
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6_Very_StrongBP7
The NM_031475.3(ESPN):c.1080G>A(p.Thr360=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000044 in 1,614,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000042 ( 0 hom. )
Consequence
ESPN
NM_031475.3 synonymous
NM_031475.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.74
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 Benign. Variant got -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
?
Variant 1-6444570-G-A is Benign according to our data. Variant chr1-6444570-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 227357.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.74 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ESPN | NM_031475.3 | c.1080G>A | p.Thr360= | synonymous_variant | 6/13 | ENST00000645284.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ESPN | ENST00000645284.1 | c.1080G>A | p.Thr360= | synonymous_variant | 6/13 | NM_031475.3 | P1 | ||
ENST00000419034.1 | n.215+992C>T | intron_variant, non_coding_transcript_variant | 5 | ||||||
ESPN | ENST00000636330.1 | c.1080G>A | p.Thr360= | synonymous_variant | 6/11 | 5 | |||
ESPN | ENST00000418286.1 | c.435G>A | p.Thr145= | synonymous_variant | 4/5 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000591 AC: 9AN: 152198Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251456Hom.: 0 AF XY: 0.0000441 AC XY: 6AN XY: 135902
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GnomAD4 exome AF: 0.0000424 AC: 62AN: 1461884Hom.: 0 Cov.: 32 AF XY: 0.0000413 AC XY: 30AN XY: 727242
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GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152198Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74342
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 04, 2016 | p.Thr360Thr in exon 6 of ESPN: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 5/66702 of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitu te.org;dbSNP rs373242735). - |
ESPN-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 15, 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). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | May 15, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at