rs150820026
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001127198.5(TMC6):c.1842C>T(p.Pro614=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000119 in 1,603,258 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00056 ( 2 hom., cov: 32)
Exomes 𝑓: 0.000073 ( 1 hom. )
Consequence
TMC6
NM_001127198.5 synonymous
NM_001127198.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -5.25
Genes affected
TMC6 (HGNC:18021): (transmembrane channel like 6) 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 10 transmembrane domains and 2 leucine zipper motifs. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
?
Variant 17-78119016-G-A is Benign according to our data. Variant chr17-78119016-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 526250.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-5.25 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000558 (85/152282) while in subpopulation AFR AF= 0.00183 (76/41566). AF 95% confidence interval is 0.0015. There are 2 homozygotes in gnomad4. There are 50 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMC6 | NM_001127198.5 | c.1842C>T | p.Pro614= | synonymous_variant | 15/20 | ENST00000590602.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMC6 | ENST00000590602.6 | c.1842C>T | p.Pro614= | synonymous_variant | 15/20 | 2 | NM_001127198.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000506 AC: 77AN: 152162Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000149 AC: 34AN: 228884Hom.: 0 AF XY: 0.000153 AC XY: 19AN XY: 124520
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GnomAD4 exome AF: 0.0000731 AC: 106AN: 1450976Hom.: 1 Cov.: 33 AF XY: 0.0000638 AC XY: 46AN XY: 720988
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GnomAD4 genome ? AF: 0.000558 AC: 85AN: 152282Hom.: 2 Cov.: 32 AF XY: 0.000672 AC XY: 50AN XY: 74452
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2023 | TMC6: BP4, BP7 - |
Epidermodysplasia verruciformis Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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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