NM_014233.4:c.2061C>G

Variant names:

• chr17-44207562-G-C
• rs142426190
• NM_014233.4:c.2061C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_014233.4(UBTF):​c.2061C>G​(p.Asp687Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,614,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D687D) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: UBTF NM_014233.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.83
• 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)

MIR6782 (HGNC:50270): (microRNA 6782) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.020358235).
• BS2: High AC in GnomAd4 at 5 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.2061C>G	p.Asp687Glu	missense	Exon 20 of 21	NP_055048.1	P17480-1
	UBTF	NM_001076683.2		c.1950C>G	p.Asp650Glu	missense	Exon 19 of 20	NP_001070151.1	P17480-2
	UBTF	NM_001076684.3		c.1950C>G	p.Asp650Glu	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.2061C>G	p.Asp687Glu	missense	Exon 20 of 21	ENSP00000390669.1	P17480-1
	UBTF	ENST00000529383.5	TSL:1	c.2061C>G	p.Asp687Glu	missense	Exon 19 of 20	ENSP00000435708.1	P17480-1
	UBTF	ENST00000343638.9	TSL:1	c.1950C>G	p.Asp650Glu	missense	Exon 19 of 20	ENSP00000345297.5	P17480-2

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152092 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000121

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251264 AF XY: 0.00000736

Gnomad AFR exome AF: 0.000123

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461836 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727222

African (AFR) AF: 0.0000896 AC: 3 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111982

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

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152210 Hom.: 0 Cov.: 31 AF XY: 0.0000403 AC XY: 3 AN XY: 74412

African (AFR) AF: 0.000120 AC: 5 AN: 41516

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	0.0030
DANN	Benign	0.60
DEOGEN2	Benign	0.081	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.55	T
M_CAP	Pathogenic	0.30	D
MetaRNN	Benign	0.020	T
MetaSVM	Uncertain	0.056	D
MutationAssessor	Benign	0.0	N
PhyloP100		-4.8
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.28	N
REVEL	Uncertain	0.33
Sift	Benign	1.0	T
Sift4G	Benign	0.85	T
Polyphen		0.0	B
Vest4		0.17
MutPred		0.15		Gain of helix (P = 0.0425)
MVP		0.53
MPC		0.23
ClinPred		0.035	T
GERP RS		-10
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.087
gMVP		0.026
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs142426190; hg19: chr17-42284930;