Variant 7-45105454-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000258770.8(TBRG4):c.722G>A(p.Arg241His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000281 in 1,601,400 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

TBRG4
ENST00000258770.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.90

Variant links:

Genes affected

TBRG4 (HGNC:17443): (transforming growth factor beta regulator 4) Enables RNA binding activity. Involved in mitochondrial mRNA processing and regulation of mitochondrial mRNA stability. Located in mitochondrial matrix. [provided by Alliance of Genome Resources, Apr 2022]

TBRG4 links:

TBRG4 (HGNC:):

TBRG4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.099024266).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBRG4	NM_004749.4 linkuse as main transcript	c.722G>A	p.Arg241His	missense_variant	3/11	ENST00000258770.8	NP_004740.2	Q969Z0-1
TBRG4	NM_001261834.2 linkuse as main transcript	c.755G>A	p.Arg252His	missense_variant	3/11		NP_001248763.1	B3KRS4B4DU42
TBRG4	NM_030900.4 linkuse as main transcript	c.722G>A	p.Arg241His	missense_variant	3/9		NP_112162.1	Q969Z0-2
TBRG4	NM_199122.3 linkuse as main transcript	c.722G>A	p.Arg241His	missense_variant	3/9		NP_954573.1	Q969Z0-2B3KM73

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBRG4	ENST00000258770.8 linkuse as main transcript	c.722G>A	p.Arg241His	missense_variant	3/11	1	NM_004749.4	ENSP00000258770.3		Q969Z0-1

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000495

AC:

AN:

242246

Hom.:

AF XY:

0.0000459

AC XY:

AN XY:

130634

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0000347

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000553

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000248

AC:

AN:

1449038

Hom.:

Cov.:

AF XY:

0.0000264

AC XY:

AN XY:

719014

show subpopulations

Gnomad4 AFR exome

AF:

0.0000601

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000395

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000263

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152362

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000187

Hom.:

Bravo

AF:

0.0000491

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 04, 2023

The c.722G>A (p.R241H) alteration is located in exon 3 (coding exon 2) of the TBRG4 gene. This alteration results from a G to A substitution at nucleotide position 722, causing the arginine (R) at amino acid position 241 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

T;.;.;T;T;.

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.82

.;.;T;D;D;T

M_CAP

Benign

0.0098

MetaRNN

Benign

0.099

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.79

N;N;N;N

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-3.1

D;D;D;D;D;D

REVEL

Benign

0.066

Sift

Benign

0.077

T;T;T;T;T;T

Sift4G

Benign

0.080

T;T;T;T;.;.

Polyphen

0.40

B;D;D;B;.;.

Vest4

0.29

MVP

0.13

MPC

0.34

ClinPred

0.16

GERP RS

0.79

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.7

Varity_R

0.056

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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