1-246541046-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_022366.3(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 NM_022366.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.320

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]

ACMG classification

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 GnomAdExome at 6 AR gene

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00329 AC: 501 AN: 152072 Hom.: 1 Cov.: 33

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.: 6 AF XY: 0.00325 AC XY: 437 AN XY: 134422

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.: 12 Cov.: 31 AF XY: 0.00332 AC XY: 2408 AN XY: 725410

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.: 1 Cov.: 33 AF XY: 0.00331 AC XY: 246 AN XY: 74394

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.: 3

Bravo AF: 0.00281

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00433

EpiControl AF: 0.00406

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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

Other links and lift over

dbSNP: rs143882766; hg19: chr1-246704348;