rs199502924
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM1BP4
The NM_031475.3(ESPN):c.1025C>T(p.Ser342Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000904 in 1,614,224 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. S342S) has been classified as Likely benign.
Frequency
Consequence
NM_031475.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ESPN | NM_031475.3 | c.1025C>T | p.Ser342Phe | missense_variant | 6/13 | ENST00000645284.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ESPN | ENST00000645284.1 | c.1025C>T | p.Ser342Phe | missense_variant | 6/13 | NM_031475.3 | P1 | ||
ENST00000419034.1 | n.215+1047G>A | intron_variant, non_coding_transcript_variant | 5 | ||||||
ESPN | ENST00000636330.1 | c.1025C>T | p.Ser342Phe | missense_variant | 6/11 | 5 | |||
ESPN | ENST00000418286.1 | c.380C>T | p.Ser127Phe | missense_variant | 4/5 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 152228Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000119 AC: 30AN: 251362Hom.: 0 AF XY: 0.000110 AC XY: 15AN XY: 135872
GnomAD4 exome AF: 0.0000889 AC: 130AN: 1461878Hom.: 1 Cov.: 32 AF XY: 0.0000798 AC XY: 58AN XY: 727242
GnomAD4 genome ? AF: 0.000105 AC: 16AN: 152346Hom.: 0 Cov.: 33 AF XY: 0.000107 AC XY: 8AN XY: 74496
ClinVar
Submissions by phenotype
not specified Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital | Jan 07, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 05, 2015 | The p.Ser342Phe variant in ESPN has not been previously reported in individuals with hearing loss, but has been identified in 8/66572 European chromosomes and 3 /11552 Latino chromosomes by the Exome Aggregation Consortium (ExAC, http://exac .broadinstitute.org; dbSNP rs199502924). Computational prediction tools and cons ervation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Ser342Phe variant is unc ertain. - |
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 23, 2023 | This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 342 of the ESPN protein (p.Ser342Phe). This variant is present in population databases (rs199502924, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with ESPN-related conditions. ClinVar contains an entry for this variant (Variation ID: 228668). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 11, 2021 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Usher syndrome, type 1M Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Jan 16, 2020 | This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PP3. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at