Genetic Variant TMC8:c.*1384A>G (chr17-78142496-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.04

Publications

8 publications found

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 Gene-Disease associations (from GenCC):

epidermodysplasia verruciformis, susceptibility to, 2
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
epidermodysplasia verruciformis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

TMC8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152468.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMC8	NM_152468.5	MANE Select	c.*1384A>G		3_prime_UTR	Exon 16 of 16	NP_689681.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TMC8	ENST00000318430.10	TSL:1 MANE Select	c.*1384A>G	3_prime_UTR	Exon 16 of 16	ENSP00000325561.4
TMC8	ENST00000589691.1	TSL:1	c.*1384A>G	3_prime_UTR	Exon 15 of 15	ENSP00000467482.1
TMC8	ENST00000972441.1		c.*1384A>G	3_prime_UTR	Exon 16 of 16	ENSP00000642500.1

Frequencies

GnomAD3 genomes

AF:

0.603

AC:

91706

AN:

152054

Hom.:

28146

Cov.:

show subpopulations

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:

AN:

142

Hom.:

Cov.:

AF XY:

0.575

AC XY:

AN XY:

106

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

0.600

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.550

AC:

AN:

120

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.603

AC:

91829

AN:

152172

Hom.:

28204

Cov.:

AF XY:

0.604

AC XY:

44959

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.691

AC:

28678

AN:

41514

American (AMR)

AF:

0.636

AC:

9719

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.647

AC:

2247

AN:

3472

East Asian (EAS)

AF:

0.435

AC:

2247

AN:

5170

South Asian (SAS)

AF:

0.547

AC:

2638

AN:

4820

European-Finnish (FIN)

AF:

0.598

AC:

6334

AN:

10592

Middle Eastern (MID)

AF:

0.738

AC:

217

AN:

294

European-Non Finnish (NFE)

AF:

0.558

AC:

37912

AN:

68000

Other (OTH)

AF:

0.614

AC:

1295

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1926

3851

5777

7702

9628

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

758

1516

2274

3032

3790

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.562

Hom.:

19214

Bravo

AF:

0.612

Asia WGS

AF:

0.528

AC:

1835

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.78

(source)

DANN

Benign

0.43

PhyloP100

-1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over