Variant 16-24789806-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_014494.4(TNRC6A):c.1164T>G(p.Ser388Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00049 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TNRC6A
NM_014494.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.28

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 -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14731309).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNRC6A	NM_014494.4 linkuse as main transcript	c.1164T>G	p.Ser388Arg	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.1164T>G	p.Ser388Arg	missense_variant	6/25	5	NM_014494.4	A2	Q8NDV7-1
TNRC6A	ENST00000491718.5 linkuse as main transcript	c.*689T>G		3_prime_UTR_variant, NMD_transcript_variant	3/22	1
TNRC6A	ENST00000315183.11 linkuse as main transcript	c.1164T>G	p.Ser388Arg	missense_variant	6/24	5		P4	Q8NDV7-6

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152200

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

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:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000489

AC:

712

AN:

1454600

Hom.:

Cov.:

AF XY:

0.000472

AC XY:

342

AN XY:

723894

show subpopulations

Gnomad4 AFR exome

AF:

0.000480

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.000584

Gnomad4 OTH exome

AF:

0.000300

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000460

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

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

Feb 22, 2023

The c.1164T>G (p.S388R) alteration is located in exon 6 (coding exon 6) of the TNRC6A gene. This alteration results from a T to G substitution at nucleotide position 1164, causing the serine (S) at amino acid position 388 to be replaced by an arginine (R). 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

Uncertain

0.35

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

Cadd

Benign

Dann

Uncertain

0.98

Eigen

Benign

-0.17

Eigen_PC

Benign

0.018

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.94

D;D

M_CAP

Benign

0.0063

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;L

MutationTaster

Benign

0.85

N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.027

Sift

Benign

0.039

D;D

Sift4G

Uncertain

0.015

D;D

Polyphen

0.14

B;B

Vest4

0.48

MutPred

0.25

Gain of methylation at S388 (P = 0.0458);Gain of methylation at S388 (P = 0.0458);

MVP

0.20

MPC

0.12

ClinPred

0.47

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.28

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over