chr17-44207325-C-G

Variant names:

• chr17-44207325-C-G
• rs1352360561
• NM_014233.4:c.2212G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014233.4(UBTF):​c.2212G>C​(p.Asp738His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: UBTF NM_014233.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.48

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27732003).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBTF	NM_014233.4	c.2212G>C	p.Asp738His	missense_variant	Exon 21 of 21	ENST00000436088.6	NP_055048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBTF	ENST00000436088.6	c.2212G>C	p.Asp738His	missense_variant	Exon 21 of 21	2	NM_014233.4	ENSP00000390669.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Benign	22
DANN	Benign	0.75
DEOGEN2	Benign	0.11	.;T;.;T;.;.;T
Eigen	Benign	0.062
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.80	.;.;.;.;.;T;T
M_CAP	Uncertain	0.28	D
MetaRNN	Benign	0.28	T;T;T;T;T;T;T
MetaSVM	Pathogenic	1.2	D
MutationAssessor	Benign	0.0	.;N;.;N;.;.;N
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.4	N;N;N;N;N;N;N
REVEL	Uncertain	0.34
Sift	Pathogenic	0.0	D;D;D;D;D;D;D
Sift4G	Uncertain	0.0040	D;D;D;D;D;D;D
Polyphen		0.73	P;P;P;P;P;P;P
Vest4		0.23
MutPred		0.19		.;Loss of helix (P = 0.1299);.;Loss of helix (P = 0.1299);.;.;Loss of helix (P = 0.1299);
MVP		0.75
MPC		0.29
ClinPred		0.42	T
GERP RS		5.2
Varity_R		0.34
gMVP		0.014

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

Publications

LitVar

Other links and lift over

dbSNP: rs1352360561; hg19: chr17-42284693;