Variant 22-40261873-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_001162501.2(TNRC6B):c.157G>A(p.Ala53Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000946 in 1,585,254 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000098 ( 0 hom. )

Consequence

TNRC6B
NM_001162501.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.53

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 links:

LOC124905121 (HGNC:):

LOC124905121 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.34540975).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TNRC6B	NM_001162501.2 linkuse as main transcript	c.157G>A	p.Ala53Thr	missense_variant	4/23	ENST00000454349.7
LOC124905121	XR_007068107.1 linkuse as main transcript	n.304-1505C>T		intron_variant, non_coding_transcript_variant
TNRC6B	NM_015088.3 linkuse as main transcript	c.157G>A	p.Ala53Thr	missense_variant	4/21
TNRC6B	NM_001024843.2 linkuse as main transcript	c.265G>A	p.Ala89Thr	missense_variant	7/24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNRC6B	ENST00000454349.7 linkuse as main transcript	c.157G>A	p.Ala53Thr	missense_variant	4/23	2	NM_001162501.2	P3	Q9UPQ9-3
TNRC6B	ENST00000335727.13 linkuse as main transcript	c.157G>A	p.Ala53Thr	missense_variant	4/21	1			Q9UPQ9-1
TNRC6B	ENST00000402203.5 linkuse as main transcript	c.265G>A	p.Ala89Thr	missense_variant	7/24	1		A2	Q9UPQ9-2
TNRC6B	ENST00000301923.13 linkuse as main transcript	c.265G>A	p.Ala89Thr	missense_variant	7/24	5		A2	Q9UPQ9-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000410

AC:

AN:

244068

Hom.:

AF XY:

0.00000750

AC XY:

AN XY:

133250

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000917

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000977

AC:

AN:

1433092

Hom.:

Cov.:

AF XY:

0.0000141

AC XY:

AN XY:

708378

show subpopulations

Gnomad4 AFR exome

AF:

0.0000604

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000513

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000827

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Global developmental delay with speech and behavioral abnormalities

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Revvity Omics, Revvity

Sep 21, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.096

BayesDel_noAF

Benign

-0.38

Cadd

Pathogenic

Dann

Pathogenic

1.0

Eigen

Uncertain

0.61

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.91

D;.;D;D

M_CAP

Benign

0.0045

MetaRNN

Benign

0.35

T;T;T;T

MetaSVM

Benign

-1.2

MutationTaster

Benign

1.0

D;D;N;N

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.16

N;N;N;N

REVEL

Benign

0.20

Sift

Benign

0.15

T;T;D;D

Sift4G

Benign

0.58

T;T;T;T

Polyphen

0.99

D;D;D;D

Vest4

0.56

MutPred

0.12

.;.;Gain of glycosylation at A53 (P = 0.0029);Gain of glycosylation at A53 (P = 0.0029);

MVP

0.29

MPC

0.62

ClinPred

0.67

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.18

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over