rs8068430

chr17-78136611-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_152468.5(TMC8):c.1128-624T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 172,348 control chromosomes in the GnomAD database, including 3,133 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (2765 hom., cov: 33)
  • Exomes 𝑓: 0.17 (368 hom.)
• Consequence: TMC8 NM_152468.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.812

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 17-78136611-T-C is Benign according to our data. Variant chr17-78136611-T-C is described in ClinVar as [Benign]. Clinvar id is 2688349.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMC8	NM_152468.5	c.1128-624T>C		intron_variant		ENST00000318430.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMC8	ENST00000318430.10	c.1128-624T>C		intron_variant		1	NM_152468.5	P2

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28322 AN: 152082 Hom.: 2757 Cov.: 33

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.213

GnomAD4 exome AF: 0.169 AC: 3411 AN: 20148 Hom.: 368 Cov.: 0 AF XY: 0.180 AC XY: 1940 AN XY: 10778

Gnomad4 AFR exome AF: 0.126

Gnomad4 AMR exome AF: 0.147

Gnomad4 ASJ exome AF: 0.179

Gnomad4 EAS exome AF: 0.166

Gnomad4 SAS exome AF: 0.255

Gnomad4 FIN exome AF: 0.110

Gnomad4 NFE exome AF: 0.149

Gnomad4 OTH exome AF: 0.169

GnomAD4 genome AF: 0.186 AC: 28362 AN: 152200 Hom.: 2765 Cov.: 33 AF XY: 0.190 AC XY: 14126 AN XY: 74420

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.218

Alfa AF: 0.191 Hom.: 5036

Bravo AF: 0.179

Asia WGS AF: 0.267 AC: 927 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 20% of patients studied by a panel of primary immunodeficiencies. Number of patients: 19. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.39
Dann	Benign	0.34

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: rs8068430; hg19: chr17-76132692;