dbSNP rs1048591: TMC6:n.2987C>G (chr17-78107603-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000589217.1(TMC6):n.2987C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,262 control chromosomes in the GnomAD database, including 998 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 0.11 ( 998 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TMC6
ENST00000589217.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.257

Publications

6 publications found

Variant links:

Genes affected

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:

TNRC6C (HGNC:29318): (trinucleotide repeat containing adaptor 6C) Predicted to enable RNA binding activity. Involved in gene silencing by miRNA; positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay; and positive regulation of nuclear-transcribed mRNA poly(A) tail shortening. Predicted to be located in cytosol. Predicted to be active in P-body and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TNRC6C 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=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNRC6C	NM_001142640.2 link	c.*2758G>C		3_prime_UTR_variant	Exon 23 of 23	ENST00000696270.1	NP_001136112.2	Q9HCJ0
TMC6	NM_001127198.5 link	c.*5545C>G		3_prime_UTR_variant	Exon 20 of 20	ENST00000590602.6	NP_001120670.1	Q7Z403-1A0A024R8V2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TMC6	ENST00000589217.1 link	n.2987C>G	non_coding_transcript_exon_variant	Exon 2 of 2	1
TNRC6C	ENST00000696270.1 link	c.*2758G>C	3_prime_UTR_variant	Exon 23 of 23		NM_001142640.2	ENSP00000512514.1	A0A8Q3SIH5
TMC6	ENST00000590602.6 link	c.*5545C>G	3_prime_UTR_variant	Exon 20 of 20	2	NM_001127198.5	ENSP00000465261.1	Q7Z403-1

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

16051

AN:

152144

Hom.:

988

Cov.:

show subpopulations

Gnomad AFR

AF:

0.150

Gnomad AMI

AF:

0.0713

Gnomad AMR

AF:

0.137

Gnomad ASJ

AF:

0.104

Gnomad EAS

AF:

0.156

Gnomad SAS

AF:

0.129

Gnomad FIN

AF:

0.130

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0622

Gnomad OTH

AF:

0.111

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

AF:

0.106

AC:

16101

AN:

152262

Hom.:

998

Cov.:

AF XY:

0.110

AC XY:

8207

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.150

AC:

6248

AN:

41538

American (AMR)

AF:

0.137

AC:

2096

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.104

AC:

362

AN:

3472

East Asian (EAS)

AF:

0.157

AC:

812

AN:

5186

South Asian (SAS)

AF:

0.130

AC:

628

AN:

4832

European-Finnish (FIN)

AF:

0.130

AC:

1377

AN:

10592

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0622

AC:

4232

AN:

68020

Other (OTH)

AF:

0.118

AC:

250

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

744

1489

2233

2978

3722

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

182

364

546

728

910

<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:

0.0840

Hom.:

Bravo

AF:

0.111

Asia WGS

AF:

0.153

AC:

530

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.42

(source)

DANN

Benign

0.53

PhyloP100

-0.26

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over