Variant 16-24789312-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_014494.4(TNRC6A):c.670A>G(p.Asn224Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000178 in 1,614,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

TNRC6A
NM_014494.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.88

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0767293).

BS2

High AC in GnomAd at 23 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNRC6A	NM_014494.4 linkuse as main transcript	c.670A>G	p.Asn224Asp	missense_variant	6/25	ENST00000395799.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNRC6A	ENST00000395799.8 linkuse as main transcript	c.670A>G	p.Asn224Asp	missense_variant	6/25	5	NM_014494.4	A2	Q8NDV7-1
TNRC6A	ENST00000491718.5 linkuse as main transcript	c.*195A>G		3_prime_UTR_variant, NMD_transcript_variant	3/22	1
TNRC6A	ENST00000315183.11 linkuse as main transcript	c.670A>G	p.Asn224Asp	missense_variant	6/24	5		P4	Q8NDV7-6

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000160

AC:

AN:

250306

Hom.:

AF XY:

0.000147

AC XY:

AN XY:

135744

show subpopulations

Gnomad AFR exome

AF:

0.0000644

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000317

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000181

AC:

264

AN:

1461874

Hom.:

Cov.:

AF XY:

0.000184

AC XY:

134

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000207

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.000151

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000243

Hom.:

Bravo

AF:

0.000178

ESP6500AA

AF:

0.000231

AC:

ESP6500EA

AF:

0.000467

AC:

ExAC

AF:

0.000190

AC:

EpiCase

AF:

0.000545

EpiControl

AF:

0.000415

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2022

The c.670A>G (p.N224D) alteration is located in exon 6 (coding exon 6) of the TNRC6A gene. This alteration results from a A to G substitution at nucleotide position 670, causing the asparagine (N) at amino acid position 224 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.66

Cadd

Benign

Dann

Uncertain

0.99

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.16

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.71

T;T

M_CAP

Benign

0.0069

MetaRNN

Benign

0.077

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

L;L

MutationTaster

Benign

0.96

N;N

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.055

Sift

Benign

0.039

D;D

Sift4G

Benign

0.10

T;T

Polyphen

0.0

.;B

Vest4

0.14

MVP

0.40

MPC

0.10

ClinPred

0.044

GERP RS

3.5

Varity_R

0.11

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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