rs151076155
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_152468.5(TMC8):c.1364G>A(p.Arg455Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00228 in 1,613,946 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R455W) has been classified as Uncertain significance.
Frequency
Consequence
NM_152468.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMC8 | NM_152468.5 | c.1364G>A | p.Arg455Gln | missense_variant | 12/16 | ENST00000318430.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMC8 | ENST00000318430.10 | c.1364G>A | p.Arg455Gln | missense_variant | 12/16 | 1 | NM_152468.5 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00152 AC: 232AN: 152166Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00126 AC: 315AN: 250530Hom.: 0 AF XY: 0.00133 AC XY: 180AN XY: 135714
GnomAD4 exome AF: 0.00236 AC: 3446AN: 1461662Hom.: 5 Cov.: 33 AF XY: 0.00227 AC XY: 1648AN XY: 727128
GnomAD4 genome ? AF: 0.00152 AC: 232AN: 152284Hom.: 0 Cov.: 33 AF XY: 0.00144 AC XY: 107AN XY: 74444
ClinVar
Submissions by phenotype
not provided Benign:2
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Epidermodysplasia verruciformis, susceptibility to, 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago | Mar 30, 2021 | TMC8 NM_152468.4 exon 12 p.Arg455Gln (c.1364G>A): This variant has not been reported in the literature but is present in 0.2% (25/10312) of Ashkenazi Jewish alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/17-76134100-G-A?dataset=gnomad_r2_1). This variant is present in ClinVar (Variation ID: 526232). This variant amino acid glutamine (Gln) is present in 2 species (Rhesus and Macaque) is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. - |
Epidermodysplasia verruciformis, susceptibility to, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago | Feb 12, 2020 | TMC8 NM_152468.4 exon 12 p.Arg455Gln (c.1364G>A): This variant has not been reported in the literature but is present in 0.2% (25/10312) of Ashkenazi Jewish alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/17-76134100-G-A?dataset=gnomad_r2_1). This variant is present in ClinVar (Variation ID: 526232). This variant amino acid glutamine (Gln) is present in 2 species (Rhesus and Macaque) is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. - |
Epidermodysplasia verruciformis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at