Genetic Variant UBTF:p.Asp738Gly (chr17-44207324-T-C) – 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_014233.4(UBTF):c.2213A>G(p.Asp738Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D738N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 30)

Consequence

UBTF
NM_014233.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.08

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:

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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=0.21705174).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014233.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UBTF	NM_014233.4	MANE Select	c.2213A>G	p.Asp738Gly	missense	Exon 21 of 21	NP_055048.1	P17480-1
UBTF	NM_001076683.2		c.2102A>G	p.Asp701Gly	missense	Exon 20 of 20	NP_001070151.1	P17480-2
UBTF	NM_001076684.3		c.2102A>G	p.Asp701Gly	missense	Exon 20 of 20	NP_001070152.1	P17480-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UBTF	ENST00000436088.6	TSL:2 MANE Select	c.2213A>G	p.Asp738Gly	missense	Exon 21 of 21	ENSP00000390669.1	P17480-1
UBTF	ENST00000529383.5	TSL:1	c.2213A>G	p.Asp738Gly	missense	Exon 20 of 20	ENSP00000435708.1	P17480-1
UBTF	ENST00000343638.9	TSL:1	c.2102A>G	p.Asp701Gly	missense	Exon 20 of 20	ENSP00000345297.5	P17480-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.11

Eigen

Benign

-0.0061

Eigen_PC

Benign

0.021

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.79

M_CAP

Pathogenic

0.58

MetaRNN

Benign

0.22

MetaSVM

Pathogenic

0.82

MutationAssessor

Benign

0.0

PhyloP100

2.1

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.5

REVEL

Uncertain

0.34

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.016

Polyphen

0.030

Vest4

0.17

MutPred

0.19

Loss of helix (P = 0.0376)

MVP

0.75

MPC

0.32

ClinPred

0.29

GERP RS

5.2

Varity_R

0.45

gMVP

0.0098

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over