chr16-24799360-C-T

Variant names:

• chr16-24799360-C-T
• rs17177078
• NM_014494.4:c.3694+1394C>T

Variant summary

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

The NM_014494.4(TNRC6A):​c.3694+1394C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.045 in 152,270 control chromosomes in the GnomAD database, including 204 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 0.045 (204 hom., cov: 32)
• Consequence: TNRC6A NM_014494.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.191
• Publications: 24 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.062 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNRC6A	NM_014494.4	c.3694+1394C>T		intron_variant	Intron 11 of 24	ENST00000395799.8	NP_055309.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNRC6A	ENST00000395799.8	c.3694+1394C>T		intron_variant	Intron 11 of 24	5	NM_014494.4	ENSP00000379144.3

Frequencies

GnomAD3 genomes AF: 0.0450 AC: 6844 AN: 152152 Hom.: 203 Cov.: 32

Gnomad AFR AF: 0.0106

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.0439

Gnomad ASJ AF: 0.0838

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0228

Gnomad FIN AF: 0.0743

Gnomad MID AF: 0.0924

Gnomad NFE AF: 0.0636

Gnomad OTH AF: 0.0489

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

GnomAD4 genome AF: 0.0450 AC: 6845 AN: 152270 Hom.: 204 Cov.: 32 AF XY: 0.0444 AC XY: 3309 AN XY: 74454

African (AFR) AF: 0.0105 AC: 438 AN: 41546

American (AMR) AF: 0.0439 AC: 672 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0838 AC: 291 AN: 3472

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5186

South Asian (SAS) AF: 0.0230 AC: 111 AN: 4824

European-Finnish (FIN) AF: 0.0743 AC: 788 AN: 10602

Middle Eastern (MID) AF: 0.0993 AC: 29 AN: 292

European-Non Finnish (NFE) AF: 0.0636 AC: 4326 AN: 68024

Other (OTH) AF: 0.0483 AC: 102 AN: 2110

Alfa AF: 0.0550 Hom.: 615

Bravo AF: 0.0424

Asia WGS AF: 0.0160 AC: 57 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.64
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17177078; hg19: chr16-24810681;