Genetic Variant TNRC6B:p.Glu19Lys (chr22-40156124-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000402203.5(TNRC6B):c.55G>A(p.Glu19Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TNRC6B
ENST00000402203.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.14

Publications

0 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
syndromic intellectual disability
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TNRC6B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34919167).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNRC6B	NM_001024843.2 link	c.55G>A	p.Glu19Lys	missense_variant	Exon 4 of 24		NP_001020014.1	Q9UPQ9-2A0A024R1N5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNRC6B	ENST00000402203.5 link	c.55G>A	p.Glu19Lys	missense_variant	Exon 4 of 24	1		ENSP00000384795.1		Q9UPQ9-2
TNRC6B	ENST00000301923.13 link	c.55G>A	p.Glu19Lys	missense_variant	Exon 4 of 24	5		ENSP00000306759.9		Q9UPQ9-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

200526

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1428086

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

706690

African (AFR)

AF:

0.00

AC:

AN:

32880

American (AMR)

AF:

0.00

AC:

AN:

39302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25438

East Asian (EAS)

AF:

0.00

AC:

AN:

38350

South Asian (SAS)

AF:

0.00

AC:

AN:

81002

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51482

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5728

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1094610

Other (OTH)

AF:

0.00

AC:

AN:

59294

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.080

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Benign

0.25

LIST_S2

Uncertain

0.86

D;D;.

M_CAP

Benign

0.076

MetaRNN

Benign

0.35

T;T;T

MetaSVM

Benign

-0.63

PhyloP100

6.1

PROVEAN

Uncertain

-4.0

D;N;N

REVEL

Benign

0.28

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;T;T

Polyphen

0.97

.;D;D

Vest4

0.52, 0.53

MutPred

0.21

Gain of ubiquitination at E19 (P = 0.0031);Gain of ubiquitination at E19 (P = 0.0031);Gain of ubiquitination at E19 (P = 0.0031);

MVP

0.49

ClinPred

0.99

GERP RS

5.7

Mutation Taster

=82/18

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over