Variant chr17-78131402-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_152468.5(TMC8):c.-187C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0925 in 772,482 control chromosomes in the GnomAD database, including 3,569 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.081 ( 604 hom., cov: 34)

Exomes 𝑓: 0.095 ( 2965 hom. )

Consequence

TMC8
NM_152468.5 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.144

Variant links:

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]

TMC8 links:

TMC6 (HGNC:18021): (transmembrane channel like 6) 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 10 transmembrane domains and 2 leucine zipper motifs. [provided by RefSeq, Jul 2008]

TMC6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 17-78131402-C-T is Benign according to our data. Variant chr17-78131402-C-T is described in ClinVar as [Benign]. Clinvar id is 1263402.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMC8	NM_152468.5 linkuse as main transcript	c.-187C>T		5_prime_UTR_variant	2/16	ENST00000318430.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMC8	ENST00000318430.10 linkuse as main transcript	c.-187C>T		5_prime_UTR_variant	2/16	1	NM_152468.5	P2	Q8IU68-1

Frequencies

GnomAD3 genomes

AF:

0.0814

AC:

12379

AN:

152138

Hom.:

603

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0381

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.0787

Gnomad ASJ

AF:

0.107

Gnomad EAS

AF:

0.113

Gnomad SAS

AF:

0.0921

Gnomad FIN

AF:

0.107

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.100

Gnomad OTH

AF:

0.0913

GnomAD4 exome

AF:

0.0953

AC:

59078

AN:

620226

Hom.:

2965

Cov.:

AF XY:

0.0952

AC XY:

30727

AN XY:

322906

show subpopulations

Gnomad4 AFR exome

AF:

0.0329

Gnomad4 AMR exome

AF:

0.0695

Gnomad4 ASJ exome

AF:

0.101

Gnomad4 EAS exome

AF:

0.0822

Gnomad4 SAS exome

AF:

0.0914

Gnomad4 FIN exome

AF:

0.108

Gnomad4 NFE exome

AF:

0.0996

Gnomad4 OTH exome

AF:

0.0926

GnomAD4 genome

AF:

0.0813

AC:

12379

AN:

152256

Hom.:

604

Cov.:

AF XY:

0.0820

AC XY:

6104

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0380

Gnomad4 AMR

AF:

0.0788

Gnomad4 ASJ

AF:

0.107

Gnomad4 EAS

AF:

0.113

Gnomad4 SAS

AF:

0.0921

Gnomad4 FIN

AF:

0.107

Gnomad4 NFE

AF:

0.100

Gnomad4 OTH

AF:

0.0908

Alfa

AF:

0.0866

Hom.:

Bravo

AF:

0.0774

Asia WGS

AF:

0.0960

AC:

334

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

7.2

DANN

Benign

0.88

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over