Variant 7-45101537-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000258770.8(TBRG4):c.1645A>G(p.Thr549Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,508 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TBRG4
ENST00000258770.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.192

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.026144624).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBRG4	NM_004749.4 linkuse as main transcript	c.1645A>G	p.Thr549Ala	missense_variant	9/11	ENST00000258770.8	NP_004740.2	Q969Z0-1
TBRG4	NM_001261834.2 linkuse as main transcript	c.1678A>G	p.Thr560Ala	missense_variant	9/11		NP_001248763.1	B3KRS4B4DU42
TBRG4	NM_030900.4 linkuse as main transcript	c.1315A>G	p.Thr439Ala	missense_variant	7/9		NP_112162.1	Q969Z0-2
TBRG4	NM_199122.3 linkuse as main transcript	c.1315A>G	p.Thr439Ala	missense_variant	7/9		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.1645A>G	p.Thr549Ala	missense_variant	9/11	1	NM_004749.4	ENSP00000258770.3		Q969Z0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461508

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727056

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Jan 22, 2024

The c.1645A>G (p.T549A) alteration is located in exon 9 (coding exon 8) of the TBRG4 gene. This alteration results from a A to G substitution at nucleotide position 1645, causing the threonine (T) at amino acid position 549 to be replaced by an alanine (A). 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

0.054

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

1.5

DANN

Benign

0.61

DEOGEN2

Benign

0.0043

T;.;.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.42

.;.;T;T

M_CAP

Benign

0.0010

MetaRNN

Benign

0.026

T;T;T;T

MetaSVM

Benign

-0.95

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.43

N;N;N;N

REVEL

Benign

0.017

Sift

Benign

0.71

T;T;T;T

Sift4G

Benign

0.75

T;T;T;T

Polyphen

0.0

B;B;B;B

Vest4

0.084

MutPred

0.20

Loss of glycosylation at T549 (P = 0.0121);.;.;Loss of glycosylation at T549 (P = 0.0121);

MVP

0.068

MPC

0.22

ClinPred

0.042

GERP RS

-1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.015

gMVP

0.49

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over