3-33408778-A-G

Position:

• chr3-33408778-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014517.5(UBP1):​c.839T>C​(p.Ile280Thr) 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. 12/21 in silico tools predict 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: 32)
• Consequence: UBP1 NM_014517.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.47

Genes affected

UBP1 (HGNC:12507): (upstream binding protein 1) Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in negative regulation of viral transcription and positive regulation of transcription by RNA polymerase II. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

UBP1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14936051).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBP1	NM_014517.5	c.839T>C	p.Ile280Thr	missense_variant	8/16	ENST00000283629.8	NP_055332.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBP1	ENST00000283629.8	c.839T>C	p.Ile280Thr	missense_variant	8/16	1	NM_014517.5	ENSP00000283629.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 13, 2024

The c.839T>C (p.I280T) alteration is located in exon 8 (coding exon 8) of the UBP1 gene. This alteration results from a T to C substitution at nucleotide position 839, causing the isoleucine (I) at amino acid position 280 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	25
DANN	Benign	0.90
DEOGEN2	Benign	0.088	T;T
Eigen	Benign	-0.19
Eigen_PC	Benign	0.059
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	.;T
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N;N
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.85	N;N
REVEL	Benign	0.085
Sift	Benign	0.24	T;T
Sift4G	Benign	0.48	T;T
Polyphen		0.047	B;B
Vest4		0.49
MutPred		0.29		Loss of catalytic residue at I280 (P = 0.0571);Loss of catalytic residue at I280 (P = 0.0571);
MVP		0.068
MPC		1.2
ClinPred		0.72	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.062
gMVP		0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-33450270;