chr16-24643587-C-T

Variant names:

• chr16-24643587-C-T
• rs7190684
• NM_001351850.2:c.80+2578C>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.80+2578C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.717 in 151,994 control chromosomes in the GnomAD database, including 40,262 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 0.72 (40262 hom., cov: 30)
• Consequence: TNRC6A NM_001351850.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70
• Publications: 2 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 Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNRC6A	NM_001351850.2	c.80+2578C>T		intron_variant	Intron 2 of 23		NP_001338779.1
TNRC6A	XM_024450231.2	c.80+2578C>T		intron_variant	Intron 2 of 24		XP_024305999.1
TNRC6A	XM_017023144.3	c.80+2578C>T		intron_variant	Intron 2 of 23		XP_016878633.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNRC6A	ENST00000566108.2	n.402+2578C>T		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.717 AC: 108938 AN: 151876 Hom.: 40214 Cov.: 30

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.837

Gnomad AMR AF: 0.666

Gnomad ASJ AF: 0.799

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.735

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.726

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

GnomAD4 genome AF: 0.717 AC: 109038 AN: 151994 Hom.: 40262 Cov.: 30 AF XY: 0.714 AC XY: 53027 AN XY: 74290

African (AFR) AF: 0.889 AC: 36870 AN: 41474

American (AMR) AF: 0.665 AC: 10145 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.799 AC: 2773 AN: 3472

East Asian (EAS) AF: 0.417 AC: 2148 AN: 5156

South Asian (SAS) AF: 0.736 AC: 3550 AN: 4826

European-Finnish (FIN) AF: 0.591 AC: 6226 AN: 10528

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.660 AC: 44825 AN: 67968

Other (OTH) AF: 0.722 AC: 1524 AN: 2110

Alfa AF: 0.683 Hom.: 116568

Bravo AF: 0.727

Asia WGS AF: 0.639 AC: 2223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.11
DANN	Benign	0.79
PhyloP100		-1.7

Splicing

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

Other links and lift over

dbSNP: rs7190684; hg19: chr16-24654908;