chr17-78131665-T-C
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_152468.5(TMC8):c.77T>C(p.Met26Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0315 in 1,568,410 control chromosomes in the GnomAD database, including 1,013 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.024 ( 82 hom., cov: 34)
Exomes 𝑓: 0.032 ( 931 hom. )
Consequence
TMC8
NM_152468.5 missense
NM_152468.5 missense
Scores
3
10
Clinical Significance
Conservation
PhyloP100: 0.165
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]
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=0.0019472837).
BP6
?
Variant 17-78131665-T-C is Benign according to our data. Variant chr17-78131665-T-C is described in ClinVar as [Benign]. Clinvar id is 1169102.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-78131665-T-C is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0747 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMC8 | NM_152468.5 | c.77T>C | p.Met26Thr | missense_variant | 2/16 | ENST00000318430.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMC8 | ENST00000318430.10 | c.77T>C | p.Met26Thr | missense_variant | 2/16 | 1 | NM_152468.5 | P2 | |
TMC6 | ENST00000322914.7 | c.-75+676A>G | intron_variant | 1 | P1 | ||||
TMC8 | ENST00000589691.1 | c.-372+260T>C | intron_variant | 1 | A2 | ||||
TMC8 | ENST00000590799.5 | n.459T>C | non_coding_transcript_exon_variant | 2/4 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0238 AC: 3630AN: 152218Hom.: 83 Cov.: 34
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GnomAD3 exomes AF: 0.0321 AC: 5477AN: 170648Hom.: 155 AF XY: 0.0353 AC XY: 3258AN XY: 92302
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GnomAD4 exome AF: 0.0324 AC: 45814AN: 1416076Hom.: 931 Cov.: 32 AF XY: 0.0339 AC XY: 23745AN XY: 700296
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GnomAD4 genome ? AF: 0.0238 AC: 3628AN: 152334Hom.: 82 Cov.: 34 AF XY: 0.0240 AC XY: 1788AN XY: 74490
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ESP6500AA
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Asia WGS
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 09, 2018 | - - |
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
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;N
PrimateAI
Uncertain
T
Sift4G
Uncertain
D;D
Polyphen
0.0050
.;B
Vest4
0.11
MPC
1.7
ClinPred
T
GERP RS
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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