Variant 17-44207335-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_014233.4(UBTF):c.2202C>G(p.Asp734Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000416 in 1,611,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

UBTF
NM_014233.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.07

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.037154198).

BS2

High AC in GnomAd4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBTF	NM_014233.4 link	c.2202C>G	p.Asp734Glu	missense_variant	Exon 21 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.2202C>G	p.Asp734Glu	missense_variant	Exon 21 of 21	2	NM_014233.4	ENSP00000390669.1		P17480-1

Frequencies

GnomAD3 genomes

AF:

0.0000659

AC:

AN:

151744

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000324

AC:

AN:

246744

Hom.:

AF XY:

0.0000300

AC XY:

AN XY:

133358

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000719

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000391

AC:

AN:

1459366

Hom.:

Cov.:

AF XY:

0.0000441

AC XY:

AN XY:

725850

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000513

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000659

AC:

AN:

151744

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74108

show subpopulations

Gnomad4 AFR

AF:

0.0000485

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000565

Hom.:

Bravo

AF:

0.0000718

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Nov 13, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2202C>G (p.D734E) alteration is located in exon 21 (coding exon 20) of the UBTF gene. This alteration results from a C to G substitution at nucleotide position 2202, causing the aspartic acid (D) at amino acid position 734 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

0.074

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.27

CADD

Benign

0.0050

DANN

Benign

0.64

DEOGEN2

Benign

0.083

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

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.53

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

M_CAP

Uncertain

0.097

MetaRNN

Benign

0.037

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

MetaSVM

Uncertain

0.23

MutationAssessor

Benign

1.1

.;L;.;L;.;.;L

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.020

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

REVEL

Uncertain

0.32

Sift

Benign

0.62

T;D;T;D;T;T;D

Sift4G

Benign

0.83

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

Polyphen

0.0

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

Vest4

0.10

MutPred

0.12

.;Gain of helix (P = 0.0854);.;Gain of helix (P = 0.0854);.;.;Gain of helix (P = 0.0854);

MVP

0.61

MPC

0.23

ClinPred

0.035

GERP RS

-11

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.7

Varity_R

0.28

gMVP

0.0026

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