Genetic Variant TNRC6B:p.Pro55Pro (chr22-40261881-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7

The NM_001162501.2(TNRC6B):c.165A>G(p.Pro55Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000695 in 1,439,530 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

TNRC6B
NM_001162501.2 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.954

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:

ENSG00000309895 (HGNC:):

ENSG00000309895 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 22-40261881-A-G is Benign according to our data. Variant chr22-40261881-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3044680.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.954 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNRC6B	NM_001162501.2 link	c.165A>G	p.Pro55Pro	synonymous_variant	Exon 4 of 23	ENST00000454349.7	NP_001155973.1	Q9UPQ9-3
TNRC6B	NM_015088.3 link	c.165A>G	p.Pro55Pro	synonymous_variant	Exon 4 of 21		NP_055903.2	Q9UPQ9-1
TNRC6B	NM_001024843.2 link	c.273A>G	p.Pro91Pro	synonymous_variant	Exon 7 of 24		NP_001020014.1	Q9UPQ9-2A0A024R1N5
LOC124905121	XR_007068107.1 link	n.304-1513T>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNRC6B	ENST00000454349.7 link	c.165A>G	p.Pro55Pro	synonymous_variant	Exon 4 of 23	2	NM_001162501.2	ENSP00000401946.2		Q9UPQ9-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.95e-7

AC:

AN:

1439530

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

712520

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33178

American (AMR)

AF:

0.00

AC:

AN:

44474

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25872

East Asian (EAS)

AF:

0.00

AC:

AN:

39120

South Asian (SAS)

AF:

0.00

AC:

AN:

85494

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5708

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1093934

Other (OTH)

AF:

0.0000169

AC:

AN:

59130

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TNRC6B-related disorder

Benign:1

Jul 26, 2022

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

5.1

(source)

DANN

Benign

0.70

PhyloP100

-0.95

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over