rs454138

chr17-78141256-C-Gchr17-78141256-C-T

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.*144C>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 0.646 in 417,804 control chromosomes in the GnomAD database, including 88,458 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.67 (35005 hom., cov: 33)
  • Exomes 𝑓: 0.63 (53453 hom.)
• Consequence: TMC8 NM_152468.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.391

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=-0.88).
• BP6: Variant 17-78141256-C-G is Benign according to our data. Variant chr17-78141256-C-G is described in ClinVar as [Benign]. Clinvar id is 1243217.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMC8	NM_152468.5	c.*144C>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.*144C>G		3_prime_UTR_variant	16/16	1	NM_152468.5	P2

Frequencies

GnomAD3 genomes AF: 0.673 AC: 102262 AN: 152038 Hom.: 34945 Cov.: 33

Gnomad AFR AF: 0.779

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.711

Gnomad ASJ AF: 0.702

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.615

Gnomad OTH AF: 0.690

GnomAD4 exome AF: 0.631 AC: 167678 AN: 265648 Hom.: 53453 Cov.: 3 AF XY: 0.631 AC XY: 85544 AN XY: 135480

Gnomad4 AFR exome AF: 0.778

Gnomad4 AMR exome AF: 0.683

Gnomad4 ASJ exome AF: 0.720

Gnomad4 EAS exome AF: 0.522

Gnomad4 SAS exome AF: 0.601

Gnomad4 FIN exome AF: 0.659

Gnomad4 NFE exome AF: 0.627

Gnomad4 OTH exome AF: 0.653

GnomAD4 genome AF: 0.673 AC: 102384 AN: 152156 Hom.: 35005 Cov.: 33 AF XY: 0.674 AC XY: 50140 AN XY: 74382

Gnomad4 AFR AF: 0.780

Gnomad4 AMR AF: 0.711

Gnomad4 ASJ AF: 0.702

Gnomad4 EAS AF: 0.530

Gnomad4 SAS AF: 0.597

Gnomad4 FIN AF: 0.663

Gnomad4 NFE AF: 0.615

Gnomad4 OTH AF: 0.693

Alfa AF: 0.647 Hom.: 3825

Bravo AF: 0.683

Asia WGS AF: 0.596 AC: 2073 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	2.3
Dann	Benign	0.73

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: rs454138; hg19: chr17-76137337;