chr6-155299885-G-A

Variant names:

• chr6-155299885-G-A
• rs950994
• NM_016020.4:c.286-1300C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016020.4(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 NM_016020.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900
• Publications: 21 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TFB1M	NM_016020.4	c.286-1300C>T		intron_variant	Intron 2 of 6	ENST00000367166.5	NP_057104.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFB1M	ENST00000367166.5	c.286-1300C>T		intron_variant	Intron 2 of 6	1	NM_016020.4	ENSP00000356134.4
TFB1M	ENST00000470239.1	n.197+11447C>T		intron_variant	Intron 2 of 2	3
TFB1M	ENST00000475849.1	n.458-1300C>T		intron_variant	Intron 3 of 4	5
TFB1M	ENST00000487586.5	n.326-1300C>T		intron_variant	Intron 1 of 2	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

African (AFR) AF: 0.443 AC: 18361 AN: 41462

American (AMR) AF: 0.497 AC: 7588 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1117 AN: 3468

East Asian (EAS) AF: 0.656 AC: 3394 AN: 5174

South Asian (SAS) AF: 0.432 AC: 2084 AN: 4826

European-Finnish (FIN) AF: 0.305 AC: 3214 AN: 10552

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21663 AN: 67978

Other (OTH) AF: 0.380 AC: 804 AN: 2116

Alfa AF: 0.352 Hom.: 30254

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
PhyloP100		-0.090
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs950994; hg19: chr6-155621019;