Genetic Variant TBRG4:p.Ser511Thr (chr7-45101860-C-G) – 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>C(p.Ser511Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S511I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TBRG4
NM_004749.4 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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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=0.14122388).

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>C	p.Ser511Thr	missense	Exon 8 of 11	NP_004740.2
TBRG4	NM_001261834.2		c.1565G>C	p.Ser522Thr	missense	Exon 8 of 11	NP_001248763.1	B4DU42
TBRG4	NM_030900.4		c.1202G>C	p.Ser401Thr	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>C	p.Ser511Thr	missense	Exon 8 of 11	ENSP00000258770.3	Q969Z0-1
TBRG4	ENST00000361278.7	TSL:1	c.1202G>C	p.Ser401Thr	missense	Exon 6 of 9	ENSP00000354992.3	Q969Z0-2
TBRG4	ENST00000495973.5	TSL:1	n.2821G>C		non_coding_transcript_exon	Exon 6 of 9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000407

AC:

AN:

245884

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1456352

Hom.:

Cov.:

AF XY:

0.00

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:

0.0000232

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:

0.00

AC:

AN:

1111406

Other (OTH)

AF:

0.00

AC:

AN:

60246

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.020

Eigen

Benign

-0.10

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.65

M_CAP

Benign

0.0075

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

PhyloP100

4.2

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.1

REVEL

Benign

0.087

Sift

Benign

0.31

Sift4G

Benign

0.12

Polyphen

0.54

Vest4

0.17

MutPred

0.28

Loss of ubiquitination at K509 (P = 0.069)

MVP

0.15

MPC

0.35

ClinPred

0.43

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.057

gMVP

0.47

Mutation Taster

=90/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over