dbSNP rs1555582065: UBTF:p.Glu210Gln (chr17-44212851-C-G) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PM5

The NM_014233.4(UBTF):c.628G>C(p.Glu210Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,784 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. E210K) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

UBTF
NM_014233.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.53

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr17-44212851-C-T is described in ClinVar as Pathogenic/Likely_pathogenic. ClinVar VariationId is 437909.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBTF	NM_014233.4 link	c.628G>C	p.Glu210Gln	missense_variant	Exon 7 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.628G>C	p.Glu210Gln	missense_variant	Exon 7 of 21	2	NM_014233.4	ENSP00000390669.1		P17480-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461784

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727206

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111944

Other (OTH)

AF:

0.00

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.12

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.43

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

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.97

LIST_S2

Pathogenic

0.98

.;.;D;.;.;.;D;D

M_CAP

Uncertain

0.23

MetaRNN

Uncertain

0.42

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

MetaSVM

Pathogenic

0.96

MutationAssessor

Uncertain

2.3

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

PhyloP100

7.5

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.49

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

REVEL

Uncertain

0.63

Sift

Benign

0.39

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

Sift4G

Uncertain

0.058

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

Polyphen

0.41

B;D;D;B;D;B;B;D

Vest4

0.58

MutPred

0.45

Gain of MoRF binding (P = 0.0276);Gain of MoRF binding (P = 0.0276);Gain of MoRF binding (P = 0.0276);Gain of MoRF binding (P = 0.0276);Gain of MoRF binding (P = 0.0276);Gain of MoRF binding (P = 0.0276);Gain of MoRF binding (P = 0.0276);Gain of MoRF binding (P = 0.0276);

MVP

0.74

MPC

2.2

ClinPred

0.83

GERP RS

4.8

Varity_R

0.26

gMVP

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over