rs2290906

Positions:

• chr17-78097785-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001142640.2(TNRC6C):​c.4968T>C​(p.Ser1656=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,550,700 control chromosomes in the GnomAD database, including 27,346 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 (4712 hom., cov: 33)
  • Exomes 𝑓: 0.17 (22634 hom.)
• Consequence: TNRC6C NM_001142640.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.396

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP7: Synonymous conserved (PhyloP=0.396 with no splicing effect.
• 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.4968T>C	p.Ser1656=	synonymous_variant	19/23	ENST00000696270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNRC6C	ENST00000696270.1	c.4968T>C	p.Ser1656=	synonymous_variant	19/23		NM_001142640.2	P4
TNRC6C	ENST00000636222.1	c.4992T>C	p.Ser1664=	synonymous_variant	19/23	5		A2
TNRC6C	ENST00000588061.6	c.4457-558T>C		intron_variant		5
TNRC6C	ENST00000696541.1	c.4928-558T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34765 AN: 152108 Hom.: 4693 Cov.: 33

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.217

GnomAD3 exomes AF: 0.220 AC: 34418 AN: 156270 Hom.: 4389 AF XY: 0.221 AC XY: 18298 AN XY: 82766

Gnomad AFR exome AF: 0.359

Gnomad AMR exome AF: 0.290

Gnomad ASJ exome AF: 0.160

Gnomad EAS exome AF: 0.348

Gnomad SAS exome AF: 0.300

Gnomad FIN exome AF: 0.158

Gnomad NFE exome AF: 0.146

Gnomad OTH exome AF: 0.219

GnomAD4 exome AF: 0.169 AC: 236229 AN: 1398474 Hom.: 22634 Cov.: 32 AF XY: 0.172 AC XY: 118489 AN XY: 689730

Gnomad4 AFR exome AF: 0.362

Gnomad4 AMR exome AF: 0.290

Gnomad4 ASJ exome AF: 0.163

Gnomad4 EAS exome AF: 0.311

Gnomad4 SAS exome AF: 0.298

Gnomad4 FIN exome AF: 0.160

Gnomad4 NFE exome AF: 0.143

Gnomad4 OTH exome AF: 0.201

GnomAD4 genome AF: 0.229 AC: 34833 AN: 152226 Hom.: 4712 Cov.: 33 AF XY: 0.232 AC XY: 17295 AN XY: 74434

Gnomad4 AFR AF: 0.355

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.324

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.223

Alfa AF: 0.170 Hom.: 2020

Bravo AF: 0.242

Asia WGS AF: 0.347 AC: 1202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	10
DANN	Benign	0.71

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

Other links and lift over

dbSNP: rs2290906; hg19: chr17-76093866; COSMIC: COSV56940523; COSMIC: COSV56940523;