rs412611

chr17-78136178-C-T

Variant summary

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

The NM_152468.5(TMC8):c.1128-1057C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0479 in 152,158 control chromosomes in the GnomAD database, including 208 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 0.048 (208 hom., cov: 33)
• Consequence: TMC8 NM_152468.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMC8	NM_152468.5	c.1128-1057C>T		intron_variant		ENST00000318430.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMC8	ENST00000318430.10	c.1128-1057C>T		intron_variant		1	NM_152468.5	P2

Frequencies

GnomAD3 genomes AF: 0.0480 AC: 7295 AN: 152040 Hom.: 209 Cov.: 33

Gnomad AFR AF: 0.0117

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0666

Gnomad ASJ AF: 0.0579

Gnomad EAS AF: 0.0948

Gnomad SAS AF: 0.0481

Gnomad FIN AF: 0.0635

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0592

Gnomad OTH AF: 0.0655

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0479 AC: 7294 AN: 152158 Hom.: 208 Cov.: 33 AF XY: 0.0489 AC XY: 3639 AN XY: 74388

Gnomad4 AFR AF: 0.0117

Gnomad4 AMR AF: 0.0667

Gnomad4 ASJ AF: 0.0579

Gnomad4 EAS AF: 0.0944

Gnomad4 SAS AF: 0.0479

Gnomad4 FIN AF: 0.0635

Gnomad4 NFE AF: 0.0592

Gnomad4 OTH AF: 0.0648

Alfa AF: 0.0514 Hom.: 59

Bravo AF: 0.0480

Asia WGS AF: 0.0640 AC: 221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.8
Dann	Benign	0.24

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: rs412611; hg19: chr17-76132259;