ENST00000402203.5:c.46G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000402203.5(TNRC6B):c.46G>A(p.Val16Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0953 in 1,576,008 control chromosomes in the GnomAD database, including 8,048 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.069 ( 481 hom., cov: 32)

Exomes 𝑓: 0.098 ( 7567 hom. )

Consequence

TNRC6B
ENST00000402203.5 missense, splice_region

Scores

Splicing: ADA: 0.01321

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.07

Publications

23 publications found

Variant links:

Genes affected

TNRC6B (HGNC:29190): (trinucleotide repeat containing adaptor 6B) Enables RNA binding activity. Involved in regulation of gene expression. Predicted to be located in cytosol. Predicted to be active in P-body and nucleoplasm. Implicated in subserous uterine fibroid and uterine fibroid. [provided by Alliance of Genome Resources, Apr 2022]

TNRC6B Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
global developmental delay with speech and behavioral abnormalities
Inheritance: AD Classification: STRONG, MODERATE Submitted by: PanelApp Australia, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
syndromic intellectual disability
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TNRC6B links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000402203.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013531148).

BP6

Variant 22-40156115-G-A is Benign according to our data. Variant chr22-40156115-G-A is described in ClinVar as Benign. ClinVar VariationId is 1315562.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000402203.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNRC6B	NM_001024843.2		c.46G>A	p.Val16Met	missense splice_region	Exon 4 of 24	NP_001020014.1	Q9UPQ9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNRC6B	ENST00000402203.5	TSL:1	c.46G>A	p.Val16Met	missense splice_region	Exon 4 of 24	ENSP00000384795.1	Q9UPQ9-2
	TNRC6B	ENST00000301923.13	TSL:5	c.46G>A	p.Val16Met	missense splice_region	Exon 4 of 24	ENSP00000306759.9	Q9UPQ9-2

Frequencies

GnomAD3 genomes

AF:

0.0690

AC:

10499

AN:

152174

Hom.:

481

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0179

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.0595

Gnomad ASJ

AF:

0.114

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0406

Gnomad FIN

AF:

0.0707

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.0683

GnomAD2 exomes

AF:

0.0677

AC:

13201

AN:

194968

AF XY:

0.0675

show subpopulations

Gnomad AFR exome

AF:

0.0138

Gnomad AMR exome

AF:

0.0407

Gnomad ASJ exome

AF:

0.112

Gnomad EAS exome

AF:

0.000139

Gnomad FIN exome

AF:

0.0645

Gnomad NFE exome

AF:

0.0976

Gnomad OTH exome

AF:

0.0729

GnomAD4 exome

AF:

0.0981

AC:

139732

AN:

1423716

Hom.:

7567

Cov.:

AF XY:

0.0962

AC XY:

67772

AN XY:

704206

show subpopulations

African (AFR)

AF:

0.0148

AC:

484

AN:

32744

American (AMR)

AF:

0.0438

AC:

1694

AN:

38688

Ashkenazi Jewish (ASJ)

AF:

0.113

AC:

2865

AN:

25394

East Asian (EAS)

AF:

0.0000525

AC:

AN:

38088

South Asian (SAS)

AF:

0.0466

AC:

3761

AN:

80684

European-Finnish (FIN)

AF:

0.0660

AC:

3377

AN:

51202

Middle Eastern (MID)

AF:

0.0362

AC:

207

AN:

5716

European-Non Finnish (NFE)

AF:

0.112

AC:

121950

AN:

1092062

Other (OTH)

AF:

0.0912

AC:

5392

AN:

59138

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

5913

11825

17738

23650

29563

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4476

8952

13428

17904

22380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0689

AC:

10497

AN:

152292

Hom.:

481

Cov.:

AF XY:

0.0650

AC XY:

4837

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.0178

AC:

740

AN:

41572

American (AMR)

AF:

0.0594

AC:

909

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.114

AC:

394

AN:

3468

East Asian (EAS)

AF:

0.00116

AC:

AN:

5176

South Asian (SAS)

AF:

0.0406

AC:

196

AN:

4826

European-Finnish (FIN)

AF:

0.0707

AC:

750

AN:

10608

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.108

AC:

7326

AN:

68018

Other (OTH)

AF:

0.0676

AC:

143

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

510

1020

1531

2041

2551

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

252

378

504

630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0910

Hom.:

2744

Bravo

AF:

0.0655

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

TNRC6B-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

0.98

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Benign

0.091

LIST_S2

Benign

0.77

MetaRNN

Benign

0.0014

MetaSVM

Benign

-1.0

PhyloP100

3.1

PROVEAN

Benign

-1.6

REVEL

Benign

0.072

Sift

Benign

0.24

Sift4G

Benign

0.35

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=95/5

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.013

dbscSNV1_RF

Benign

0.13

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over