dbSNP rs752816528: UBTF:p.Ser709Ala (chr17-44207498-A-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014233.4(UBTF):c.2125T>G(p.Ser709Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

UBTF
NM_014233.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.58

Variant links:

Genes affected

UBTF (HGNC:12511): (upstream binding transcription factor) This gene encodes a member of the HMG-box DNA-binding protein family. The encoded protein plays a critical role in ribosomal RNA transcription as a key component of the pre-initiation complex, mediating the recruitment of RNA polymerase I to rDNA promoter regions. The encoded protein may also play important roles in chromatin remodeling and pre-rRNA processing, and its activity is regulated by both phosphorylation and acetylation. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. Pseudogenes of this gene are located on the short arm of chromosomes 3, 11 and X and the long arm of chromosome 11. [provided by RefSeq, Aug 2011]

UBTF links:

ATXN7L3-AS1 (HGNC:55298): (ATXN7L3 antisense RNA 1)

ATXN7L3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36742473).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBTF	NM_014233.4 link	c.2125T>G	p.Ser709Ala	missense_variant	Exon 20 of 21	ENST00000436088.6	NP_055048.1	P17480-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBTF	ENST00000436088.6 link	c.2125T>G	p.Ser709Ala	missense_variant	Exon 20 of 21	2	NM_014233.4	ENSP00000390669.1		P17480-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251370

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Feb 04, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2125T>G (p.S709A) alteration is located in exon 20 (coding exon 19) of the UBTF gene. This alteration results from a T to G substitution at nucleotide position 2125, causing the serine (S) at amino acid position 709 to be replaced by an alanine (A). 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

0.28

BayesDel_addAF

Uncertain

0.068

BayesDel_noAF

Uncertain

0.090

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.097

.;T;.;T;.;.;T

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.59

.;.;.;.;.;T;T

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.37

T;T;T;T;T;T;T

MetaSVM

Pathogenic

0.94

MutationAssessor

Uncertain

2.3

.;M;.;M;.;.;M

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.80

N;N;N;N;N;N;N

REVEL

Uncertain

0.62

Sift

Benign

0.097

T;T;T;T;T;T;T

Sift4G

Benign

0.064

T;T;T;T;T;T;T

Polyphen

0.97

D;P;D;P;D;D;P

Vest4

0.46

MutPred

0.31

.;Loss of phosphorylation at S709 (P = 0);.;Loss of phosphorylation at S709 (P = 0);.;.;Loss of phosphorylation at S709 (P = 0);

MVP

0.87

MPC

0.20

ClinPred

0.35

GERP RS

5.0

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.6

Varity_R

0.16

gMVP

0.069

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over