rs2290907

Positions:

• chr17-78097596-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142640.2(TNRC6C):​c.4928-149T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 561,766 control chromosomes in the GnomAD database, including 12,243 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 0.23 (4697 hom., cov: 32)
  • Exomes 𝑓: 0.18 (7546 hom.)
• Consequence: TNRC6C NM_001142640.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNRC6C	NM_001142640.2	c.4928-149T>C		intron_variant		ENST00000696270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNRC6C	ENST00000696270.1	c.4928-149T>C		intron_variant			NM_001142640.2	P4
TNRC6C	ENST00000588061.6	c.4457-747T>C		intron_variant		5
TNRC6C	ENST00000636222.1	c.4952-149T>C		intron_variant		5		A2
TNRC6C	ENST00000696541.1	c.4928-747T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34720 AN: 152010 Hom.: 4678 Cov.: 32

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.217

GnomAD4 exome AF: 0.177 AC: 72400 AN: 409638 Hom.: 7546 AF XY: 0.181 AC XY: 38674 AN XY: 214158

Gnomad4 AFR exome AF: 0.344

Gnomad4 AMR exome AF: 0.268

Gnomad4 ASJ exome AF: 0.162

Gnomad4 EAS exome AF: 0.302

Gnomad4 SAS exome AF: 0.281

Gnomad4 FIN exome AF: 0.159

Gnomad4 NFE exome AF: 0.138

Gnomad4 OTH exome AF: 0.203

GnomAD4 genome AF: 0.229 AC: 34788 AN: 152128 Hom.: 4697 Cov.: 32 AF XY: 0.232 AC XY: 17275 AN XY: 74374

Gnomad4 AFR AF: 0.354

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.322

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.222

Alfa AF: 0.202 Hom.: 753

Bravo AF: 0.242

Asia WGS AF: 0.347 AC: 1203 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.1
DANN	Benign	0.82

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

LitVar

Other links and lift over

dbSNP: rs2290907; hg19: chr17-76093677; COSMIC: COSV56952506; COSMIC: COSV56952506;