rs12449858
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001127198.5(TMC6):c.457C>T(p.Leu153Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0969 in 1,583,914 control chromosomes in the GnomAD database, including 10,482 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.093 ( 1059 hom., cov: 34)
Exomes 𝑓: 0.097 ( 9423 hom. )
Consequence
TMC6
NM_001127198.5 missense
NM_001127198.5 missense
Scores
2
6
6
Clinical Significance
Conservation
PhyloP100: 6.37
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0024380684).
BP6
?
Variant 17-78125237-G-A is Benign according to our data. Variant chr17-78125237-G-A is described in ClinVar as [Benign]. Clinvar id is 403545.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-78125237-G-A is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMC6 | NM_001127198.5 | c.457C>T | p.Leu153Phe | missense_variant | 6/20 | ENST00000590602.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMC6 | ENST00000590602.6 | c.457C>T | p.Leu153Phe | missense_variant | 6/20 | 2 | NM_001127198.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0932 AC: 14183AN: 152184Hom.: 1057 Cov.: 34
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GnomAD3 exomes AF: 0.133 AC: 26661AN: 200254Hom.: 3085 AF XY: 0.121 AC XY: 12996AN XY: 107504
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GnomAD4 exome AF: 0.0973 AC: 139322AN: 1431612Hom.: 9423 Cov.: 34 AF XY: 0.0954 AC XY: 67702AN XY: 709422
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GnomAD4 genome ? AF: 0.0931 AC: 14186AN: 152302Hom.: 1059 Cov.: 34 AF XY: 0.0967 AC XY: 7204AN XY: 74468
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316
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318
ESP6500AA
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113
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ExAC
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Asia WGS
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3478
ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
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 55% of patients studied by a panel of primary immunodeficiencies. Number of patients: 48. Only high quality variants are reported. - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 29, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 09, 2018 | This variant is associated with the following publications: (PMID: 25854761) - |
Epidermodysplasia verruciformis Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;T;.;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;M;M;M;.;.
MutationTaster
Benign
P;P;P;P;P;P
PrimateAI
Uncertain
T
Sift4G
Uncertain
D;D;D;D;.;.
Polyphen
D;D;D;D;.;.
Vest4
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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