Variant 16-24789465-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_014494.4(TNRC6A):c.823A>G(p.Asn275Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000325 in 1,614,216 control chromosomes in the GnomAD database, including 2 homozygotes. 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 0.00055 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00030 ( 2 hom. )

Consequence

TNRC6A
NM_014494.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.86

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013316631).

BS2

High AC in GnomAd at 84 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNRC6A	NM_014494.4 linkuse as main transcript	c.823A>G	p.Asn275Asp	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.823A>G	p.Asn275Asp	missense_variant	6/25	5	NM_014494.4	A2	Q8NDV7-1
TNRC6A	ENST00000491718.5 linkuse as main transcript	c.*348A>G		3_prime_UTR_variant, NMD_transcript_variant	3/22	1
TNRC6A	ENST00000315183.11 linkuse as main transcript	c.823A>G	p.Asn275Asp	missense_variant	6/24	5		P4	Q8NDV7-6

Frequencies

GnomAD3 genomes

AF:

0.000552

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00281

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:

0.000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000346

AC:

AN:

251460

Hom.:

AF XY:

0.000324

AC XY:

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00119

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000343

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000301

AC:

440

AN:

1461892

Hom.:

Cov.:

AF XY:

0.000279

AC XY:

203

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00103

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.000335

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.000551

AC:

AN:

152324

Hom.:

Cov.:

AF XY:

0.000779

AC XY:

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000245

Hom.:

Bravo

AF:

0.000472

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000214

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000237

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

Jan 03, 2024

The c.823A>G (p.N275D) 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 823, causing the asparagine (N) at amino acid position 275 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

0.084

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.74

Cadd

Benign

Dann

Uncertain

0.97

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.31

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.0042

MetaRNN

Benign

0.013

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.69

N;N

MutationTaster

Benign

0.92

N;N

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.064

Sift

Benign

0.14

T;T

Sift4G

Benign

0.15

T;T

Polyphen

0.0

B;B

Vest4

0.12

MVP

0.30

MPC

0.10

ClinPred

0.028

GERP RS

2.3

Varity_R

0.070

gMVP

0.15

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