Variant chr16-24777324-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014494.4(TNRC6A):c.555T>A(p.Asn185Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,612,918 control chromosomes in the GnomAD database, including 28,634 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.19 ( 2734 hom., cov: 32)

Exomes 𝑓: 0.19 ( 25900 hom. )

Consequence

TNRC6A
NM_014494.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.846

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.302199E-4).

BP6

Variant 16-24777324-T-A is Benign according to our data. Variant chr16-24777324-T-A is described in ClinVar as [Benign]. Clinvar id is 1279086.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNRC6A	NM_014494.4 linkuse as main transcript	c.555T>A	p.Asn185Lys	missense_variant	5/25	ENST00000395799.8	NP_055309.2	Q8NDV7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TNRC6A	ENST00000395799.8 linkuse as main transcript	c.555T>A	p.Asn185Lys	missense_variant	5/25	5	NM_014494.4	ENSP00000379144.3	Q8NDV7-1
TNRC6A	ENST00000491718.5 linkuse as main transcript	n.75T>A		non_coding_transcript_exon_variant	1/22	1		ENSP00000460688.1	I3L3S5
TNRC6A	ENST00000315183.11 linkuse as main transcript	c.555T>A	p.Asn185Lys	missense_variant	5/24	5		ENSP00000326900.7	Q8NDV7-6

Frequencies

GnomAD3 genomes

AF:

0.186

AC:

28315

AN:

152002

Hom.:

2735

Cov.:

show subpopulations

Gnomad AFR

AF:

0.213

Gnomad AMI

AF:

0.177

Gnomad AMR

AF:

0.166

Gnomad ASJ

AF:

0.141

Gnomad EAS

AF:

0.110

Gnomad SAS

AF:

0.158

Gnomad FIN

AF:

0.132

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.193

Gnomad OTH

AF:

0.199

GnomAD3 exomes

AF:

0.172

AC:

42857

AN:

248664

Hom.:

3852

AF XY:

0.171

AC XY:

23142

AN XY:

135022

show subpopulations

Gnomad AFR exome

AF:

0.214

Gnomad AMR exome

AF:

0.168

Gnomad ASJ exome

AF:

0.157

Gnomad EAS exome

AF:

0.108

Gnomad SAS exome

AF:

0.148

Gnomad FIN exome

AF:

0.137

Gnomad NFE exome

AF:

0.193

Gnomad OTH exome

AF:

0.173

GnomAD4 exome

AF:

0.186

AC:

272146

AN:

1460798

Hom.:

25900

Cov.:

AF XY:

0.185

AC XY:

134267

AN XY:

726750

show subpopulations

Gnomad4 AFR exome

AF:

0.207

Gnomad4 AMR exome

AF:

0.167

Gnomad4 ASJ exome

AF:

0.154

Gnomad4 EAS exome

AF:

0.102

Gnomad4 SAS exome

AF:

0.151

Gnomad4 FIN exome

AF:

0.137

Gnomad4 NFE exome

AF:

0.195

Gnomad4 OTH exome

AF:

0.184

GnomAD4 genome

AF:

0.186

AC:

28310

AN:

152120

Hom.:

2734

Cov.:

AF XY:

0.180

AC XY:

13375

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.213

Gnomad4 AMR

AF:

0.166

Gnomad4 ASJ

AF:

0.141

Gnomad4 EAS

AF:

0.109

Gnomad4 SAS

AF:

0.158

Gnomad4 FIN

AF:

0.132

Gnomad4 NFE

AF:

0.193

Gnomad4 OTH

AF:

0.197

Alfa

AF:

0.193

Hom.:

2173

Bravo

AF:

0.189

TwinsUK

AF:

0.195

AC:

724

ALSPAC

AF:

0.196

AC:

754

ESP6500AA

AF:

0.189

AC:

770

ESP6500EA

AF:

0.187

AC:

1574

ExAC

AF:

0.174

AC:

21086

Asia WGS

AF:

0.139

AC:

486

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 11, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Epilepsy, familial adult myoclonic, 6

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.59

DEOGEN2

Benign

0.014

.;T

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.39

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.88

D;D

MetaRNN

Benign

0.00093

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.0

N;N

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.88

N;N

REVEL

Benign

0.089

Sift

Benign

0.090

T;T

Sift4G

Benign

0.25

T;T

Polyphen

0.0

.;B

Vest4

0.082

MutPred

0.075

Gain of ubiquitination at N185 (P = 0.0029);Gain of ubiquitination at N185 (P = 0.0029);

MPC

0.10

ClinPred

0.0025

GERP RS

2.4

Varity_R

0.049

gMVP

0.14

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over