rs950994

Positions:

• chr6-155299885-G-A

Variant summary

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

The ENST00000367166.5(TFB1M):​c.286-1300C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 152,046 control chromosomes in the GnomAD database, including 11,900 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 0.39 (11900 hom., cov: 32)
• Consequence: TFB1M ENST00000367166.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFB1M	NM_016020.4	c.286-1300C>T		intron_variant		ENST00000367166.5	NP_057104.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFB1M	ENST00000367166.5	c.286-1300C>T		intron_variant		1	NM_016020.4	ENSP00000356134	P1
TFB1M	ENST00000470239.1	n.197+11447C>T		intron_variant, non_coding_transcript_variant		3
TFB1M	ENST00000475849.1	n.458-1300C>T		intron_variant, non_coding_transcript_variant		5
TFB1M	ENST00000487586.5	n.326-1300C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58514 AN: 151928 Hom.: 11867 Cov.: 32

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.377

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

GnomAD4 genome AF: 0.385 AC: 58598 AN: 152046 Hom.: 11900 Cov.: 32 AF XY: 0.388 AC XY: 28809 AN XY: 74324

Gnomad4 AFR AF: 0.443

Gnomad4 AMR AF: 0.497

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.656

Gnomad4 SAS AF: 0.432

Gnomad4 FIN AF: 0.305

Gnomad4 NFE AF: 0.319

Gnomad4 OTH AF: 0.380

Alfa AF: 0.343 Hom.: 17683

Bravo AF: 0.408

Asia WGS AF: 0.529 AC: 1837 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.20
DANN	Benign	0.60

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: rs950994; hg19: chr6-155621019;