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GeneBe

16-24777228-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_014494.4(TNRC6A):c.459G>A(p.Gln153=) 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

2

Clinical Significance

Benign criteria provided, single submitter B:1

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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=2.45 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
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
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1646 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TNRC6ANM_014494.4 linkuse as main transcriptc.459G>A p.Gln153= synonymous_variant 5/25 ENST00000395799.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TNRC6AENST00000395799.8 linkuse as main transcriptc.459G>A p.Gln153= synonymous_variant 5/255 NM_014494.4 A2Q8NDV7-1
TNRC6AENST00000315183.11 linkuse as main transcriptc.459G>A p.Gln153= synonymous_variant 5/245 P4Q8NDV7-6
TNRC6AENST00000491718.5 linkuse as main transcript upstream_gene_variant 1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0108
AC:
1646
AN:
152170
Hom.:
18
Cov.:
32
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.:
17
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.:
35
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0108
AC:
1646
AN:
152288
Hom.:
18
Cov.:
32
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.:
32
Bravo
AF:
0.0123
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.0126
EpiControl
AF:
0.0146

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

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.

Other links and lift over

dbSNP: rs117821015; hg19: chr16-24788549; COSMIC: COSV59370479; COSMIC: COSV59370479; API