Genetic Variant BTF3:p.Arg13Trp (chr5-73498704-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001037637.2(BTF3):c.37C>T(p.Arg13Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,343,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

BTF3
NM_001037637.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.449

Publications

0 publications found

Variant links:

Genes affected

BTF3 (HGNC:1125): (basic transcription factor 3) This gene encodes the basic transcription factor 3. This protein forms a stable complex with RNA polymerase IIB and is required for transcriptional initiation. Alternative splicing results in multiple transcript variants encoding different isoforms. This gene has multiple pseudogenes. [provided by RefSeq, Jul 2008]

BTF3 links:

BTF3-DT (HGNC:55211): (BTF3 divergent transcript)

BTF3-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13881832).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BTF3	NM_001037637.2 link	c.37C>T	p.Arg13Trp	missense_variant	Exon 1 of 6	ENST00000380591.8	NP_001032726.1	P20290-1
BTF3	NM_001393652.1 link	c.37C>T	p.Arg13Trp	missense_variant	Exon 1 of 5		NP_001380581.1
BTF3	NM_001207.5 link	c.-1+146C>T		intron_variant	Intron 1 of 5		NP_001198.2	P20290-2
BTF3	NM_001393653.1 link	c.-1+146C>T		intron_variant	Intron 1 of 4		NP_001380582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BTF3	ENST00000380591.8 link	c.37C>T	p.Arg13Trp	missense_variant	Exon 1 of 6	1	NM_001037637.2	ENSP00000369965.3		P20290-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000102

AC:

AN:

97632

AF XY:

0.0000184

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000175

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1343990

Hom.:

Cov.:

AF XY:

0.0000121

AC XY:

AN XY:

663434

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26900

American (AMR)

AF:

0.00

AC:

AN:

23828

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22470

East Asian (EAS)

AF:

0.0000920

AC:

AN:

32614

South Asian (SAS)

AF:

0.0000133

AC:

AN:

74960

European-Finnish (FIN)

AF:

0.0000257

AC:

AN:

38854

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5194

European-Non Finnish (NFE)

AF:

0.0000150

AC:

AN:

1063542

Other (OTH)

AF:

0.0000180

AC:

AN:

55628

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 10, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.37C>T (p.R13W) alteration is located in exon 1 (coding exon 1) of the BTF3 gene. This alteration results from a C to T substitution at nucleotide position 37, causing the arginine (R) at amino acid position 13 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.039

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.77

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PhyloP100

0.45

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-0.21

REVEL

Benign

0.085

Sift

Pathogenic

0.0

Sift4G

Benign

0.11

Polyphen

0.0

Vest4

0.16

MutPred

0.23

Loss of methylation at R13 (P = 0.0085);

MVP

0.26

MPC

1.9

ClinPred

0.88

GERP RS

3.7

PromoterAI

-0.040

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.30

gMVP

0.22

Mutation Taster

=92/8

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

5-73498704-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over