Genetic Variant TBRG4:p.Ser511Ile (chr7-45101860-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004749.4(TBRG4):c.1532G>T(p.Ser511Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000046 in 1,456,352 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.000046 ( 0 hom. )

Consequence

TBRG4
NM_004749.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.17

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18502301).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004749.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TBRG4	NM_004749.4	MANE Select	c.1532G>T	p.Ser511Ile	missense	Exon 8 of 11	NP_004740.2
TBRG4	NM_001261834.2		c.1565G>T	p.Ser522Ile	missense	Exon 8 of 11	NP_001248763.1	B4DU42
TBRG4	NM_030900.4		c.1202G>T	p.Ser401Ile	missense	Exon 6 of 9	NP_112162.1	Q969Z0-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TBRG4	ENST00000258770.8	TSL:1 MANE Select	c.1532G>T	p.Ser511Ile	missense	Exon 8 of 11	ENSP00000258770.3	Q969Z0-1
TBRG4	ENST00000361278.7	TSL:1	c.1202G>T	p.Ser401Ile	missense	Exon 6 of 9	ENSP00000354992.3	Q969Z0-2
TBRG4	ENST00000495973.5	TSL:1	n.2821G>T		non_coding_transcript_exon	Exon 6 of 9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000244

AC:

AN:

245884

AF XY:

0.0000150

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000534

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000460

AC:

AN:

1456352

Hom.:

Cov.:

AF XY:

0.0000359

AC XY:

AN XY:

724722

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33290

American (AMR)

AF:

0.00

AC:

AN:

43832

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26014

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.00

AC:

AN:

86186

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50176

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5514

European-Non Finnish (NFE)

AF:

0.0000567

AC:

AN:

1111406

Other (OTH)

AF:

0.0000664

AC:

AN:

60246

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000672

Hom.:

Bravo

AF:

0.0000189

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.031

Eigen

Benign

0.057

Eigen_PC

Benign

-0.017

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.73

M_CAP

Benign

0.018

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.77

PhyloP100

4.2

PrimateAI

Benign

0.35

PROVEAN

Benign

-2.2

REVEL

Benign

0.094

Sift

Benign

0.12

Sift4G

Uncertain

0.022

Polyphen

0.74

Vest4

0.27

MutPred

0.36

Loss of disorder (P = 0.0098)

MVP

0.093

MPC

0.68

ClinPred

0.41

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.088

gMVP

0.58

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over