rs11654773

Positions:

• chr17-78141852-T-G

Variant summary

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

The NM_152468.5(TMC8):​c.*740T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0606 in 152,380 control chromosomes in the GnomAD database, including 409 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 0.061 (409 hom., cov: 34)
  • Exomes 𝑓: 0.025 (0 hom.)
• Consequence: TMC8 NM_152468.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0580

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMC8	NM_152468.5	c.*740T>G		3_prime_UTR_variant	16/16	ENST00000318430.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMC8	ENST00000318430.10	c.*740T>G		3_prime_UTR_variant	16/16	1	NM_152468.5	P2

Frequencies

GnomAD3 genomes AF: 0.0605 AC: 9210 AN: 152222 Hom.: 410 Cov.: 34

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0457

Gnomad ASJ AF: 0.0447

Gnomad EAS AF: 0.00807

Gnomad SAS AF: 0.0962

Gnomad FIN AF: 0.0214

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0380

Gnomad OTH AF: 0.0550

GnomAD4 exome AF: 0.0250 AC: 1 AN: 40 Hom.: 0 Cov.: 0 AF XY: 0.0357 AC XY: 1 AN XY: 28

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0385

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0606 AC: 9231 AN: 152340 Hom.: 409 Cov.: 34 AF XY: 0.0605 AC XY: 4511 AN XY: 74502

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.0456

Gnomad4 ASJ AF: 0.0447

Gnomad4 EAS AF: 0.00809

Gnomad4 SAS AF: 0.0963

Gnomad4 FIN AF: 0.0214

Gnomad4 NFE AF: 0.0380

Gnomad4 OTH AF: 0.0563

Alfa AF: 0.0426 Hom.: 157

Bravo AF: 0.0622

Asia WGS AF: 0.0630 AC: 217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.0
DANN	Benign	0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs11654773; hg19: chr17-76137933;