17-78142496-A-G

Position:

• chr17-78142496-A-G

Variant summary

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

The NM_152468.5(TMC8):​c.*1384A>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 0.603 in 152,314 control chromosomes in the GnomAD database, including 28,227 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 0.60 (28204 hom., cov: 34)
  • Exomes 𝑓: 0.58 (23 hom.)
• Consequence: TMC8 NM_152468.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMC8	NM_152468.5	c.*1384A>G		3_prime_UTR_variant	16/16	ENST00000318430.10	NP_689681.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMC8	ENST00000318430.10	c.*1384A>G		3_prime_UTR_variant	16/16	1	NM_152468.5	ENSP00000325561.4
TMC8	ENST00000589691.1	c.*1384A>G		3_prime_UTR_variant	15/15	1		ENSP00000467482.1

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91706 AN: 152054 Hom.: 28146 Cov.: 34

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.594

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.609

GnomAD4 exome AF: 0.577 AC: 82 AN: 142 Hom.: 23 Cov.: 0 AF XY: 0.575 AC XY: 61 AN XY: 106

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.600

Gnomad4 NFE exome AF: 0.550

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.603 AC: 91829 AN: 152172 Hom.: 28204 Cov.: 34 AF XY: 0.604 AC XY: 44959 AN XY: 74388

Gnomad4 AFR AF: 0.691

Gnomad4 AMR AF: 0.636

Gnomad4 ASJ AF: 0.647

Gnomad4 EAS AF: 0.435

Gnomad4 SAS AF: 0.547

Gnomad4 FIN AF: 0.598

Gnomad4 NFE AF: 0.558

Gnomad4 OTH AF: 0.614

Alfa AF: 0.545 Hom.: 10125

Bravo AF: 0.612

Asia WGS AF: 0.528 AC: 1835 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.78
DANN	Benign	0.43

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: rs4789015; hg19: chr17-76138577;