chr17-44207459-C-A

Variant names:

• chr17-44207459-C-A
• rs483352703
• NM_014233.4:c.2164G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_014233.4(UBTF):​c.2164G>T​(p.Asp722Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 30)
• Consequence: UBTF NM_014233.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided P:1 U:1
• Conservation: PhyloP100: 6.34
• Publications: 1 publications found

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]

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

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBTF	NM_014233.4	MANE Select	c.2164G>T	p.Asp722Tyr	missense	Exon 20 of 21	NP_055048.1	P17480-1
	UBTF	NM_001076683.2		c.2053G>T	p.Asp685Tyr	missense	Exon 19 of 20	NP_001070151.1	P17480-2
	UBTF	NM_001076684.3		c.2053G>T	p.Asp685Tyr	missense	Exon 19 of 20	NP_001070152.1	P17480-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBTF	ENST00000436088.6	TSL:2 MANE Select	c.2164G>T	p.Asp722Tyr	missense	Exon 20 of 21	ENSP00000390669.1	P17480-1
	UBTF	ENST00000529383.5	TSL:1	c.2164G>T	p.Asp722Tyr	missense	Exon 19 of 20	ENSP00000435708.1	P17480-1
	UBTF	ENST00000343638.9	TSL:1	c.2053G>T	p.Asp685Tyr	missense	Exon 19 of 20	ENSP00000345297.5	P17480-2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 30

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	1	-	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	34
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.84	T
M_CAP	Pathogenic	0.36	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Benign	1.7	L
PhyloP100		6.3
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.52
Sift	Benign	0.059	T
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.58
MutPred		0.25		Gain of phosphorylation at D722 (P = 0.0013)
MVP		0.67
MPC		0.30
ClinPred		0.91	D
GERP RS		5.0
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.61
gMVP		0.058

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.99		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.99		Position offset: 2

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

Other links and lift over

dbSNP: rs483352703; hg19: chr17-42284827;