1-246564370-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.378C>T(p.Asp126=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00909 in 1,614,032 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0065 (5 hom., cov: 33)
  • Exomes 𝑓: 0.0094 (82 hom.)
• Consequence: TFB2M NM_022366.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.116

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=-0.81).
• BP6: Variant 1-246564370-G-A is Benign according to our data. Variant chr1-246564370-G-A is described in ClinVar as [Benign]. Clinvar id is 717695.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.116 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TFB2M	NM_022366.3	c.378C>T	p.Asp126=	synonymous_variant	2/8	ENST00000366514.5
TFB2M	XM_011544248.2	c.378C>T	p.Asp126=	synonymous_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFB2M	ENST00000366514.5	c.378C>T	p.Asp126=	synonymous_variant	2/8	1	NM_022366.3	P1

Frequencies

GnomAD3 genomes AF: 0.00653 AC: 994 AN: 152194 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.00222

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00635

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00497

Gnomad FIN AF: 0.00188

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0109

Gnomad OTH AF: 0.00718

GnomAD3 exomes AF: 0.00630 AC: 1584 AN: 251454 Hom.: 13 AF XY: 0.00657 AC XY: 893 AN XY: 135902

Gnomad AFR exome AF: 0.00178

Gnomad AMR exome AF: 0.00266

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00630

Gnomad FIN exome AF: 0.00199

Gnomad NFE exome AF: 0.0104

Gnomad OTH exome AF: 0.00684

GnomAD4 exome AF: 0.00936 AC: 13685 AN: 1461720 Hom.: 82 Cov.: 30 AF XY: 0.00911 AC XY: 6627 AN XY: 727166

Gnomad4 AFR exome AF: 0.00134

Gnomad4 AMR exome AF: 0.00304

Gnomad4 ASJ exome AF: 0.000230

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00623

Gnomad4 FIN exome AF: 0.00273

Gnomad4 NFE exome AF: 0.0111

Gnomad4 OTH exome AF: 0.00740

GnomAD4 genome AF: 0.00651 AC: 991 AN: 152312 Hom.: 5 Cov.: 33 AF XY: 0.00604 AC XY: 450 AN XY: 74476

Gnomad4 AFR AF: 0.00221

Gnomad4 AMR AF: 0.00634

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00476

Gnomad4 FIN AF: 0.00188

Gnomad4 NFE AF: 0.0109

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.00849 Hom.: 5

Bravo AF: 0.00722

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.00938

EpiControl AF: 0.0103

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 31, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.78
Dann	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs34587495; hg19: chr1-246727672;