Variant 1-246541046-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The ENST00000366514.5(TFB2M):c.1176C>T(p.Thr392=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00326 in 1,610,744 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0033 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0033 ( 12 hom. )

Consequence

TFB2M
ENST00000366514.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.320

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 1-246541046-G-A is Benign according to our data. Variant chr1-246541046-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2640234.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.32 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFB2M	NM_022366.3 linkuse as main transcript	c.1176C>T	p.Thr392=	synonymous_variant	8/8	ENST00000366514.5	NP_071761.1
TFB2M	XM_011544248.2 linkuse as main transcript	c.873C>T	p.Thr291=	synonymous_variant	6/6		XP_011542550.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFB2M	ENST00000366514.5 linkuse as main transcript	c.1176C>T	p.Thr392=	synonymous_variant	8/8	1	NM_022366.3	ENSP00000355471	P1

Frequencies

GnomAD3 genomes

AF:

0.00329

AC:

501

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000628

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00548

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00526

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00320

AC:

795

AN:

248726

Hom.:

AF XY:

0.00325

AC XY:

437

AN XY:

134422

show subpopulations

Gnomad AFR exome

AF:

0.000435

Gnomad AMR exome

AF:

0.00204

Gnomad ASJ exome

AF:

0.00190

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000100

Gnomad FIN exome

AF:

0.00653

Gnomad NFE exome

AF:

0.00478

Gnomad OTH exome

AF:

0.00265

GnomAD4 exome

AF:

0.00326

AC:

4755

AN:

1458554

Hom.:

Cov.:

AF XY:

0.00332

AC XY:

2408

AN XY:

725410

show subpopulations

Gnomad4 AFR exome

AF:

0.000420

Gnomad4 AMR exome

AF:

0.00205

Gnomad4 ASJ exome

AF:

0.00138

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000467

Gnomad4 FIN exome

AF:

0.00733

Gnomad4 NFE exome

AF:

0.00366

Gnomad4 OTH exome

AF:

0.00246

GnomAD4 genome

AF:

0.00329

AC:

501

AN:

152190

Hom.:

Cov.:

AF XY:

0.00331

AC XY:

246

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.000626

Gnomad4 AMR

AF:

0.00275

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00548

Gnomad4 NFE

AF:

0.00526

Gnomad4 OTH

AF:

0.00614

Alfa

AF:

0.00460

Hom.:

Bravo

AF:

0.00281

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00433

EpiControl

AF:

0.00406

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

TFB2M: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.92

DANN

Benign

0.45

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