Variant chr16-24777228-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_014494.4(TNRC6A):c.459G>A(p.Gln153Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 1,614,178 control chromosomes in the GnomAD database, including 140 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 18 hom., cov: 32)

Exomes 𝑓: 0.012 ( 122 hom. )

Consequence

TNRC6A
NM_014494.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.45

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 16-24777228-G-A is Benign according to our data. Variant chr16-24777228-G-A is described in ClinVar as [Benign]. Clinvar id is 781725.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.45 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0108 (1646/152288) while in subpopulation AMR AF= 0.0197 (301/15300). AF 95% confidence interval is 0.0178. There are 18 homozygotes in gnomad4. There are 796 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1646 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNRC6A	NM_014494.4 linkuse as main transcript	c.459G>A	p.Gln153Gln	synonymous_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.459G>A	p.Gln153Gln	synonymous_variant	5/25	5	NM_014494.4	ENSP00000379144.3	Q8NDV7-1
TNRC6A	ENST00000315183.11 linkuse as main transcript	c.459G>A	p.Gln153Gln	synonymous_variant	5/24	5		ENSP00000326900.7	Q8NDV7-6
TNRC6A	ENST00000491718.5 linkuse as main transcript	n.-22G>A		upstream_gene_variant		1		ENSP00000460688.1	I3L3S5

Frequencies

GnomAD3 genomes

AF:

0.0108

AC:

1646

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00905

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0197

Gnomad ASJ

AF:

0.00950

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00217

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0127

Gnomad OTH

AF:

0.0158

GnomAD3 exomes

AF:

0.00883

AC:

2207

AN:

249986

Hom.:

AF XY:

0.00872

AC XY:

1183

AN XY:

135602

show subpopulations

Gnomad AFR exome

AF:

0.00980

Gnomad AMR exome

AF:

0.0123

Gnomad ASJ exome

AF:

0.00784

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00356

Gnomad FIN exome

AF:

0.00195

Gnomad NFE exome

AF:

0.0116

Gnomad OTH exome

AF:

0.0135

GnomAD4 exome

AF:

0.0116

AC:

16901

AN:

1461890

Hom.:

122

Cov.:

AF XY:

0.0114

AC XY:

8259

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00953

Gnomad4 AMR exome

AF:

0.0123

Gnomad4 ASJ exome

AF:

0.00815

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00378

Gnomad4 FIN exome

AF:

0.00277

Gnomad4 NFE exome

AF:

0.0131

Gnomad4 OTH exome

AF:

0.0118

GnomAD4 genome

AF:

0.0108

AC:

1646

AN:

152288

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

796

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00905

Gnomad4 AMR

AF:

0.0197

Gnomad4 ASJ

AF:

0.00950

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.00217

Gnomad4 NFE

AF:

0.0127

Gnomad4 OTH

AF:

0.0156

Alfa

AF:

0.0125

Hom.:

Bravo

AF:

0.0123

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0126

EpiControl

AF:

0.0146

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

9.1

DANN

Benign

0.73

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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