1-246556683-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_022366.3(TFB2M):​c.595G>A​(p.Gly199Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000007 in 1,428,524 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

TFB2M
NM_022366.3 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.475
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.046789736).
BP6
Variant 1-246556683-C-T is Benign according to our data. Variant chr1-246556683-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3806287.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TFB2MNM_022366.3 linkc.595G>A p.Gly199Ser missense_variant Exon 4 of 8 ENST00000366514.5 NP_071761.1 Q9H5Q4
TFB2MXM_011544248.2 linkc.403-5381G>A intron_variant Intron 2 of 5 XP_011542550.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TFB2MENST00000366514.5 linkc.595G>A p.Gly199Ser missense_variant Exon 4 of 8 1 NM_022366.3 ENSP00000355471.4 Q9H5Q4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.00e-7
AC:
1
AN:
1428524
Hom.:
0
Cov.:
30
AF XY:
0.00000141
AC XY:
1
AN XY:
710252
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000261
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Jan 01, 2025
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
0.17
DANN
Benign
0.49
DEOGEN2
Benign
0.012
T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.0046
N
LIST_S2
Benign
0.27
T
M_CAP
Benign
0.0053
T
MetaRNN
Benign
0.047
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
-0.20
N
PrimateAI
Benign
0.29
T
PROVEAN
Benign
0.83
N
REVEL
Benign
0.022
Sift
Benign
0.41
T
Sift4G
Benign
0.37
T
Polyphen
0.0020
B
Vest4
0.21
MutPred
0.49
Gain of disorder (P = 0.0608);
MVP
0.24
MPC
0.15
ClinPred
0.025
T
GERP RS
1.4
Varity_R
0.034
gMVP
0.38

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.

Other links and lift over

dbSNP: rs1383497401; hg19: chr1-246719985; API