17-44207524-C-T

Position:

chr17-44207524-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_014233.4(UBTF):c.2099G>A(p.Gly700Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

UBTF
NM_014233.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.45

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;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), UBTF. . Gene score misZ 4.7489 (greater than the threshold 3.09). Trascript score misZ 6.257 (greater than threshold 3.09). GenCC has associacion of gene with childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder.

BP4

Computational evidence support a benign effect (MetaRNN=0.09297559).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBTF	NM_014233.4 linkuse as main transcript	c.2099G>A	p.Gly700Glu	missense_variant	20/21	ENST00000436088.6	NP_055048.1
ATXN7L3-AS1	NR_184071.1 linkuse as main transcript	n.91+8594C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBTF	ENST00000436088.6 linkuse as main transcript	c.2099G>A	p.Gly700Glu	missense_variant	20/21	2	NM_014233.4	ENSP00000390669	P1	P17480-1
ATXN7L3-AS1	ENST00000586560.1 linkuse as main transcript	n.54-8567C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251374

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

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:

0.00000205

AC:

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 10, 2023

The c.2099G>A (p.G700E) alteration is located in exon 20 (coding exon 19) of the UBTF gene. This alteration results from a G to A substitution at nucleotide position 2099, causing the glycine (G) at amino acid position 700 to be replaced by a glutamic acid (E). 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

-0.016

BayesDel_noAF

Benign

-0.090

CADD

Benign

DANN

Benign

0.73

DEOGEN2

Benign

0.079

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

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.80

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

M_CAP

Uncertain

0.097

MetaRNN

Benign

0.093

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

MetaSVM

Uncertain

0.71

MutationAssessor

Benign

-0.60

.;N;.;N;.;.;N

MutationTaster

Benign

0.76

D;D;D;D;N;N;N;N

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.13

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

REVEL

Uncertain

0.31

Sift

Pathogenic

0.0

D;D;D;D;D;D;D

Sift4G

Benign

1.0

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

Polyphen

0.023

B;B;B;B;B;B;B

Vest4

0.32

MutPred

0.21

.;Gain of solvent accessibility (P = 0.0281);.;Gain of solvent accessibility (P = 0.0281);.;.;Gain of solvent accessibility (P = 0.0281);

MVP

0.31

MPC

0.49

ClinPred

0.43

GERP RS

4.1

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.7

Varity_R

0.19

gMVP

0.088

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