Variant 1-246544548-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_022366.3(TFB2M):c.992G>A(p.Arg331His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000255 in 1,607,670 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

TFB2M
NM_022366.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.31

Variant links:

Genes affected

TFB2M (HGNC:18559): (transcription factor B2, mitochondrial) Enables mitochondrial transcription factor activity. Involved in transcription initiation from mitochondrial promoter. Located in mitochondrial nucleoid. [provided by Alliance of Genome Resources, Apr 2022]

TFB2M links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1

In a mutagenesis_site Impairs transcription initiation; when associated with A-330. (size 0) in uniprot entity TFB2M_HUMAN

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TFB2M	NM_022366.3 linkuse as main transcript	c.992G>A	p.Arg331His	missense_variant	7/8	ENST00000366514.5
TFB2M	XM_011544248.2 linkuse as main transcript	c.689G>A	p.Arg230His	missense_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFB2M	ENST00000366514.5 linkuse as main transcript	c.992G>A	p.Arg331His	missense_variant	7/8	1	NM_022366.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000163

AC:

AN:

245046

Hom.:

AF XY:

0.0000227

AC XY:

AN XY:

132412

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:

0.000139

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000275

AC:

AN:

1455522

Hom.:

Cov.:

AF XY:

0.0000262

AC XY:

AN XY:

723894

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000233

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000166

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000162

Gnomad4 OTH exome

AF:

0.0000831

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

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

Nov 01, 2022

The c.992G>A (p.R331H) alteration is located in exon 7 (coding exon 7) of the TFB2M gene. This alteration results from a G to A substitution at nucleotide position 992, causing the arginine (R) at amino acid position 331 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

0.23

BayesDel_addAF

Benign

-0.080

BayesDel_noAF

Benign

-0.35

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.17

Eigen

Uncertain

0.31

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.56

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.67

MetaSVM

Benign

-0.83

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

0.98

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.27

Sift

Benign

0.045

Sift4G

Benign

0.086

Polyphen

1.0

Vest4

0.40

MutPred

0.79

Loss of methylation at R331 (P = 0.0223);

MVP

0.68

MPC

0.74

ClinPred

0.92

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.28

gMVP

0.67

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