rs454138
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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.*144C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 417,804 control chromosomes in the GnomAD database, including 88,458 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.67 ( 35005 hom., cov: 33)
Exomes 𝑓: 0.63 ( 53453 hom. )
Consequence
TMC8
NM_152468.5 3_prime_UTR
NM_152468.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.391
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=-0.88).
BP6
?
Variant 17-78141256-C-G is Benign according to our data. Variant chr17-78141256-C-G is described in ClinVar as [Benign]. Clinvar id is 1243217.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMC8 | NM_152468.5 | c.*144C>G | 3_prime_UTR_variant | 16/16 | ENST00000318430.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMC8 | ENST00000318430.10 | c.*144C>G | 3_prime_UTR_variant | 16/16 | 1 | NM_152468.5 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.673 AC: 102262AN: 152038Hom.: 34945 Cov.: 33
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GnomAD4 exome AF: 0.631 AC: 167678AN: 265648Hom.: 53453 Cov.: 3 AF XY: 0.631 AC XY: 85544AN XY: 135480
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GnomAD4 genome ? AF: 0.673 AC: 102384AN: 152156Hom.: 35005 Cov.: 33 AF XY: 0.674 AC XY: 50140AN XY: 74382
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 09, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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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