rs8068430
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_152468.5(TMC8):c.1128-624T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 172,348 control chromosomes in the GnomAD database, including 3,133 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.19 ( 2765 hom., cov: 33)
Exomes 𝑓: 0.17 ( 368 hom. )
Consequence
TMC8
NM_152468.5 intron
NM_152468.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.812
Genes affected
TMC8 (HGNC:20474): (transmembrane channel like 8) Epidermodysplasia verruciformis (EV) is an autosomal recessive dermatosis characterized by abnormal susceptibility to human papillomaviruses (HPVs) and a high rate of progression to squamous cell carcinoma on sun-exposed skin. EV is caused by mutations in either of two adjacent genes located on chromosome 17q25.3. Both of these genes encode integral membrane proteins that localize to the endoplasmic reticulum and are predicted to form transmembrane channels. This gene encodes a transmembrane channel-like protein with 8 predicted transmembrane domains and 3 leucine zipper motifs. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
Variant 17-78136611-T-C is Benign according to our data. Variant chr17-78136611-T-C is described in ClinVar as [Benign]. Clinvar id is 2688349.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMC8 | NM_152468.5 | c.1128-624T>C | intron_variant | ENST00000318430.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMC8 | ENST00000318430.10 | c.1128-624T>C | intron_variant | 1 | NM_152468.5 | P2 |
Frequencies
GnomAD3 genomes AF: 0.186 AC: 28322AN: 152082Hom.: 2757 Cov.: 33
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GnomAD4 exome AF: 0.169 AC: 3411AN: 20148Hom.: 368 Cov.: 0 AF XY: 0.180 AC XY: 1940AN XY: 10778
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GnomAD4 genome AF: 0.186 AC: 28362AN: 152200Hom.: 2765 Cov.: 33 AF XY: 0.190 AC XY: 14126AN XY: 74420
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Jan 24, 2024 | This variant is classified as Benign based on local population frequency. This variant was detected in 20% of patients studied by a panel of primary immunodeficiencies. Number of patients: 19. Only high quality variants are reported. - |
Computational scores
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DANN
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at