17-78141256-C-T

Variant names:

• chr17-78141256-C-T
• rs454138
• NM_152468.5:c.*144C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152468.5(TMC8):​c.*144C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TMC8 NM_152468.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.391
• Publications: 6 publications found

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]

TMC8 Gene-Disease associations (from GenCC):

• epidermodysplasia verruciformis, susceptibility to, 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P
• epidermodysplasia verruciformis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152468.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMC8	NM_152468.5	MANE Select	c.*144C>T		3_prime_UTR	Exon 16 of 16	NP_689681.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMC8	ENST00000318430.10	TSL:1 MANE Select	c.*144C>T		3_prime_UTR	Exon 16 of 16	ENSP00000325561.4	Q8IU68-1
	TMC8	ENST00000589691.1	TSL:1	c.*144C>T		3_prime_UTR	Exon 15 of 15	ENSP00000467482.1	Q8IU68-2
	TMC8	ENST00000972441.1		c.*144C>T		3_prime_UTR	Exon 16 of 16	ENSP00000642500.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 265770 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 135542

African (AFR) AF: 0.00 AC: 0 AN: 7224

American (AMR) AF: 0.00 AC: 0 AN: 8384

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9522

East Asian (EAS) AF: 0.00 AC: 0 AN: 23794

South Asian (SAS) AF: 0.00 AC: 0 AN: 6196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22004

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1404

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 169632

Other (OTH) AF: 0.00 AC: 0 AN: 17610

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 3825

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.8
DANN	Benign	0.93
PhyloP100		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs454138; hg19: chr17-76137337;