6-155257999-C-G

Variant names:

• chr6-155257999-C-G
• NM_016020.4:c.878G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016020.4(TFB1M):​c.878G>C​(p.Arg293Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,888 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TFB1M NM_016020.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.555

Genes affected

TFB1M (HGNC:17037): (transcription factor B1, mitochondrial) The protein encoded by this gene is a dimethyltransferase that methylates the conserved stem loop of mitochondrial 12S rRNA. The encoded protein also is part of the basal mitochondrial transcription complex and is necessary for mitochondrial gene expression. The methylation and transcriptional activities of this protein are independent of one another. Variations in this gene may influence the severity of aminoglycoside-induced deafness (AID).[provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.099618256).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFB1M	NM_016020.4	c.878G>C	p.Arg293Pro	missense_variant	Exon 7 of 7	ENST00000367166.5	NP_057104.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFB1M	ENST00000367166.5	c.878G>C	p.Arg293Pro	missense_variant	Exon 7 of 7	1	NM_016020.4	ENSP00000356134.4
TFB1M	ENST00000495806.1	n.422G>C		non_coding_transcript_exon_variant	Exon 3 of 3	3
TFB1M	ENST00000468889.5	n.366-91G>C		intron_variant	Intron 3 of 3	3
TFB1M	ENST00000470239.1	n.198-91G>C		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461888 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	12
DANN	Benign	0.87
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.081	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.3	L
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.084
Sift	Benign	0.20	T
Sift4G	Benign	0.21	T
Polyphen		0.0010	B
Vest4		0.22
MutPred		0.66		Gain of catalytic residue at P292 (P = 0.0134);
MVP		0.13
MPC		0.12
ClinPred		0.049	T
GERP RS		0.79
Varity_R		0.66
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-155579133;