rs721101

chr6-155311710-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016020.4(TFB1M):c.134-371A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,242 control chromosomes in the GnomAD database, including 3,103 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (3103 hom., cov: 33)
• Consequence: TFB1M NM_016020.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TFB1M	NM_016020.4	c.134-371A>G		intron_variant		ENST00000367166.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFB1M	ENST00000367166.5	c.134-371A>G		intron_variant		1	NM_016020.4	P1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28537 AN: 152124 Hom.: 3106 Cov.: 33

Gnomad AFR AF: 0.0864

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.171

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.187 AC: 28533 AN: 152242 Hom.: 3103 Cov.: 33 AF XY: 0.184 AC XY: 13695 AN XY: 74426

Gnomad4 AFR AF: 0.0864

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.184

Gnomad4 NFE AF: 0.258

Gnomad4 OTH AF: 0.168

Alfa AF: 0.235 Hom.: 6026

Bravo AF: 0.178

Asia WGS AF: 0.168 AC: 585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.050
Dann	Benign	0.33

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: rs721101; hg19: chr6-155632844;