rs201039625

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_152468.5(TMC8):ā€‹c.141C>Gā€‹(p.Arg47Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000219 in 1,584,020 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…).

Frequency

Genomes: š‘“ 0.00017 ( 1 hom., cov: 33)
Exomes š‘“: 0.00022 ( 5 hom. )

Consequence

TMC8
NM_152468.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.309
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
Variant 17-78131729-C-G is Benign according to our data. Variant chr17-78131729-C-G is described in ClinVar as [Benign]. Clinvar id is 526247.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.309 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000171 (26/152322) while in subpopulation SAS AF= 0.00373 (18/4832). AF 95% confidence interval is 0.00241. There are 1 homozygotes in gnomad4. There are 16 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TMC8NM_152468.5 linkuse as main transcriptc.141C>G p.Arg47Arg synonymous_variant 2/16 ENST00000318430.10 NP_689681.2 Q8IU68-1A0A024R8N8B3KXZ8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TMC8ENST00000318430.10 linkuse as main transcriptc.141C>G p.Arg47Arg synonymous_variant 2/161 NM_152468.5 ENSP00000325561.4 Q8IU68-1
TMC6ENST00000322914.7 linkuse as main transcriptc.-75+612G>C intron_variant 1 ENSP00000313408.2 Q7Z403-1
TMC8ENST00000589691.1 linkuse as main transcriptc.-372+324C>G intron_variant 1 ENSP00000467482.1 Q8IU68-2
TMC8ENST00000590799.5 linkuse as main transcriptn.523C>G non_coding_transcript_exon_variant 2/45

Frequencies

GnomAD3 genomes
AF:
0.000171
AC:
26
AN:
152204
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00372
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000377
AC:
71
AN:
188538
Hom.:
0
AF XY:
0.000503
AC XY:
52
AN XY:
103370
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000344
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00238
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000113
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000224
AC:
321
AN:
1431698
Hom.:
5
Cov.:
32
AF XY:
0.000300
AC XY:
213
AN XY:
709608
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000992
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00236
Gnomad4 FIN exome
AF:
0.0000208
Gnomad4 NFE exome
AF:
0.0000983
Gnomad4 OTH exome
AF:
0.000169
GnomAD4 genome
AF:
0.000171
AC:
26
AN:
152322
Hom.:
1
Cov.:
33
AF XY:
0.000215
AC XY:
16
AN XY:
74476
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000653
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00373
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000561
Hom.:
0
Bravo
AF:
0.0000642
Asia WGS
AF:
0.00115
AC:
4
AN:
3476

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Epidermodysplasia verruciformis Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 12, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.57
CADD
Benign
14
DANN
Benign
0.82

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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.

Other links and lift over

dbSNP: rs201039625; hg19: chr17-76127810; API