rs1048591

Positions:

• chr17-78107603-G-C

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
TNRC6C	NM_001142640.2	c.*2758G>C		3_prime_UTR_variant	23/23	ENST00000696270.1	NP_001136112.2
TMC6	NM_001127198.5	c.*5545C>G		3_prime_UTR_variant	20/20	ENST00000590602.6	NP_001120670.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNRC6C	ENST00000696270.1	c.*2758G>C		3_prime_UTR_variant	23/23		NM_001142640.2	ENSP00000512514.1
TMC6	ENST00000590602	c.*5545C>G		3_prime_UTR_variant	20/20	2	NM_001127198.5	ENSP00000465261.1
TMC6	ENST00000589217.1	n.2987C>G		non_coding_transcript_exon_variant	2/2	1

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

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.157

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.0622

Gnomad4 OTH AF: 0.118

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.42
DANN	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1048591; hg19: chr17-76103684;