17-78107603-G-C

Variant names:

• chr17-78107603-G-C
• rs1048591
• NM_001142640.2:c.*2758G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142640.2(TNRC6C):​c.*2758G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 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: TNRC6C NM_001142640.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.257
• Publications: 6 publications found

Genes affected

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]

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 Gene-Disease associations (from GenCC):

• epidermodysplasia verruciformis, susceptibility to, 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)
• epidermodysplasia verruciformis

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142640.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNRC6C	NM_001142640.2	MANE Select	c.*2758G>C		3_prime_UTR	Exon 23 of 23	NP_001136112.2	Q9HCJ0-3
	TMC6	NM_001127198.5	MANE Select	c.*5545C>G		3_prime_UTR	Exon 20 of 20	NP_001120670.1	Q7Z403-1
	TNRC6C	NM_001395509.1		c.*2758G>C		3_prime_UTR	Exon 22 of 22	NP_001382438.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNRC6C	ENST00000696270.1	MANE Select	c.*2758G>C		3_prime_UTR	Exon 23 of 23	ENSP00000512514.1	Q9HCJ0-3
	TMC6	ENST00000590602.6	TSL:2 MANE Select	c.*5545C>G		3_prime_UTR	Exon 20 of 20	ENSP00000465261.1	Q7Z403-1
	TMC6	ENST00000589217.1	TSL:1	n.2987C>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.105 AC: 16051 AN: 152144 Hom.: 988 Cov.: 33

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: 0 AN: 12 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.106 AC: 16101 AN: 152262 Hom.: 998 Cov.: 33 AF XY: 0.110 AC XY: 8207 AN XY: 74458

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: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0622 AC: 4232 AN: 68020

Other (OTH) AF: 0.118 AC: 250 AN: 2116

Alfa AF: 0.0840 Hom.: 84

Bravo AF: 0.111

Asia WGS AF: 0.153 AC: 530 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.42
DANN	Benign	0.53
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1048591; hg19: chr17-76103684;