16-24718450-C-T

Variant names:

• chr16-24718450-C-T
• rs766181
• NM_001351850.2:c.81-32276C>T

Variant summary

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

The NM_001351850.2(TNRC6A):​c.81-32276C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 151,984 control chromosomes in the GnomAD database, including 5,371 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 0.25 (5371 hom., cov: 31)
• Consequence: TNRC6A NM_001351850.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.143
• Publications: 3 publications found

Genes affected

TNRC6A (HGNC:11969): (trinucleotide repeat containing adaptor 6A) This gene encodes a member of the trinucleotide repeat containing 6 protein family. The protein functions in post-transcriptional gene silencing through the RNA interference (RNAi) and microRNA pathways. The protein associates with messenger RNAs and Argonaute proteins in cytoplasmic bodies known as GW-bodies or P-bodies. Inhibiting expression of this gene delocalizes other GW-body proteins and impairs RNAi and microRNA-induced gene silencing. [provided by RefSeq, Jul 2008]

TNRC6A Gene-Disease associations (from GenCC):

• epilepsy, familial adult myoclonic, 6

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001351850.2. 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
	TNRC6A	NM_001351850.2		c.81-32276C>T		intron	N/A	NP_001338779.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNRC6A	ENST00000566108.2	TSL:3	n.403-32276C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38587 AN: 151866 Hom.: 5370 Cov.: 31

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.224

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.254 AC: 38598 AN: 151984 Hom.: 5371 Cov.: 31 AF XY: 0.247 AC XY: 18367 AN XY: 74264

African (AFR) AF: 0.228 AC: 9450 AN: 41458

American (AMR) AF: 0.182 AC: 2767 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 800 AN: 3470

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5184

South Asian (SAS) AF: 0.120 AC: 575 AN: 4810

European-Finnish (FIN) AF: 0.278 AC: 2936 AN: 10548

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.314 AC: 21373 AN: 67964

Other (OTH) AF: 0.221 AC: 467 AN: 2110

Alfa AF: 0.278 Hom.: 5268

Bravo AF: 0.244

Asia WGS AF: 0.0590 AC: 206 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	11
DANN	Benign	0.57
PhyloP100		0.14

Splicing

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

Other links and lift over

dbSNP: rs766181; hg19: chr16-24729771;