rs9807014

chr17-78112556-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001127198.5(TMC6):c.*592G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 163,356 control chromosomes in the GnomAD database, including 2,295 homozygotes. 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: 𝑓 0.15 (2114 hom., cov: 33)
  • Exomes 𝑓: 0.17 (181 hom.)
• Consequence: TMC6 NM_001127198.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMC6	NM_001127198.5	c.*592G>A		3_prime_UTR_variant	20/20	ENST00000590602.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMC6	ENST00000590602.6	c.*592G>A		3_prime_UTR_variant	20/20	2	NM_001127198.5	P1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23605 AN: 152196 Hom.: 2112 Cov.: 33

Gnomad AFR AF: 0.0737

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.178

GnomAD4 exome AF: 0.173 AC: 1909 AN: 11040 Hom.: 181 Cov.: 0 AF XY: 0.172 AC XY: 1022 AN XY: 5926

Gnomad4 AFR exome AF: 0.0781

Gnomad4 AMR exome AF: 0.182

Gnomad4 ASJ exome AF: 0.230

Gnomad4 EAS exome AF: 0.244

Gnomad4 SAS exome AF: 0.190

Gnomad4 FIN exome AF: 0.188

Gnomad4 NFE exome AF: 0.161

Gnomad4 OTH exome AF: 0.174

GnomAD4 genome AF: 0.155 AC: 23605 AN: 152316 Hom.: 2114 Cov.: 33 AF XY: 0.157 AC XY: 11720 AN XY: 74474

Gnomad4 AFR AF: 0.0735

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.179

Alfa AF: 0.178 Hom.: 3206

Bravo AF: 0.152

Asia WGS AF: 0.180 AC: 625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.6
Dann	Benign	0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs9807014; hg19: chr17-76108637;