rs1054670510

Variant names:

• chr17-44207480-C-G
• rs1054670510
• NM_014233.4:c.2143G>C

Your query was ambiguous. Multiple possible variants found:

• chr17-44207480-C-G
• chr17-44207480-C-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_014233.4(UBTF):​c.2143G>C​(p.Glu715Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000109 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. E715K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: UBTF NM_014233.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.62
• Publications: 0 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.36269483).
• BS2: High AC in GnomAdExome4 at 16 AD gene.

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.2143G>C	p.Glu715Gln	missense	Exon 20 of 21	NP_055048.1	P17480-1
	UBTF	NM_001076683.2		c.2032G>C	p.Glu678Gln	missense	Exon 19 of 20	NP_001070151.1	P17480-2
	UBTF	NM_001076684.3		c.2032G>C	p.Glu678Gln	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.2143G>C	p.Glu715Gln	missense	Exon 20 of 21	ENSP00000390669.1	P17480-1
	UBTF	ENST00000529383.5	TSL:1	c.2143G>C	p.Glu715Gln	missense	Exon 19 of 20	ENSP00000435708.1	P17480-1
	UBTF	ENST00000343638.9	TSL:1	c.2032G>C	p.Glu678Gln	missense	Exon 19 of 20	ENSP00000345297.5	P17480-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251256 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000109 AC: 16 AN: 1461862 Hom.: 0 Cov.: 33 AF XY: 0.0000151 AC XY: 11 AN XY: 727234

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000144 AC: 16 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.096	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.83	T
M_CAP	Pathogenic	0.35	D
MetaRNN	Benign	0.36	T
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Benign	1.7	L
PhyloP100		4.6
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.39	N
REVEL	Uncertain	0.49
Sift	Benign	0.061	T
Sift4G	Uncertain	0.040	D
Polyphen		0.97	D
Vest4		0.38
MutPred		0.12		Loss of stability (P = 0.1481)
MVP		0.86
MPC		0.24
ClinPred		0.77	D
GERP RS		5.0
Varity_R		0.47
gMVP		0.035
Mutation Taster		=74/26	polymorphism

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

Other links and lift over

dbSNP: rs1054670510; hg19: chr17-42284848;