rs76467743
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_152468.5(TMC8):c.1209G>A(p.Lys403=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 1,614,012 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0052 ( 9 hom., cov: 33)
Exomes 𝑓: 0.00058 ( 5 hom. )
Consequence
TMC8
NM_152468.5 synonymous
NM_152468.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.60
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 -16 ACMG points.
BP6
?
Variant 17-78137316-G-A is Benign according to our data. Variant chr17-78137316-G-A is described in ClinVar as [Benign]. Clinvar id is 526246.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00525 (799/152312) while in subpopulation AFR AF= 0.0178 (738/41550). AF 95% confidence interval is 0.0167. There are 9 homozygotes in gnomad4. There are 386 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 9 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMC8 | NM_152468.5 | c.1209G>A | p.Lys403= | synonymous_variant | 10/16 | ENST00000318430.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMC8 | ENST00000318430.10 | c.1209G>A | p.Lys403= | synonymous_variant | 10/16 | 1 | NM_152468.5 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00526 AC: 800AN: 152194Hom.: 9 Cov.: 33
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GnomAD3 exomes AF: 0.00130 AC: 328AN: 251342Hom.: 2 AF XY: 0.00100 AC XY: 136AN XY: 135894
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GnomAD4 exome AF: 0.000581 AC: 849AN: 1461700Hom.: 5 Cov.: 31 AF XY: 0.000523 AC XY: 380AN XY: 727128
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GnomAD4 genome ? AF: 0.00525 AC: 799AN: 152312Hom.: 9 Cov.: 33 AF XY: 0.00518 AC XY: 386AN XY: 74482
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
TMC8-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 06, 2023 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Epidermodysplasia verruciformis Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: 42
Find out detailed SpliceAI scores and Pangolin per-transcript scores at