dbSNP rs866332460: 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:

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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

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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