rs950821297

Variant names:

• chr6-155257942-T-A
• rs950821297
• NM_016020.4:c.935A>T

Your query was ambiguous. Multiple possible variants found:

• chr6-155257942-T-A
• chr6-155257942-T-C
• chr6-155257942-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016020.4(TFB1M):​c.935A>T​(p.Asp312Val) 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 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D312G) has been classified as Uncertain significance.

• 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: 2.40
• Publications: 0 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]

TIAM2 (HGNC:11806): (TIAM Rac1 associated GEF 2) This gene encodes a guanine nucleotide exchange factor. A highly similar mouse protein specifically activates ras-related C3 botulinum substrate 1, converting this Rho-like guanosine triphosphatase (GTPase) from a guanosine diphosphate-bound inactive state to a guanosine triphosphate-bound active state. The encoded protein may play a role in neural cell development. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28216773).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016020.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFB1M	NM_016020.4	MANE Select	c.935A>T	p.Asp312Val	missense	Exon 7 of 7	NP_057104.2	E5KTM5
	TFB1M	NM_001350502.2		c.650A>T	p.Asp217Val	missense	Exon 7 of 7	NP_001337431.1
	TFB1M	NM_001350501.2		c.795-34A>T		intron	N/A	NP_001337430.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFB1M	ENST00000367166.5	TSL:1 MANE Select	c.935A>T	p.Asp312Val	missense	Exon 7 of 7	ENSP00000356134.4	Q8WVM0
	TFB1M	ENST00000909440.1		c.1109A>T	p.Asp370Val	missense	Exon 7 of 7	ENSP00000579499.1
	TFB1M	ENST00000929540.1		c.1037A>T	p.Asp346Val	missense	Exon 8 of 8	ENSP00000599599.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461890 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Benign	0.78
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.032
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		2.4
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.14
Sift	Benign	0.25	T
Sift4G	Benign	0.20	T
Polyphen		0.15	B
Vest4		0.49
MutPred		0.47		Loss of solvent accessibility (P = 0.0299)
MVP		0.44
MPC		0.14
ClinPred		0.35	T
GERP RS		5.9
Varity_R		0.43
gMVP		0.42
Mutation Taster		=70/30	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs950821297; hg19: chr6-155579076;