1-209830967-A-C

Variant names:

• chr1-209830967-A-C
• NM_014388.7:c.312A>C
• UTP25 p.Glu104Asp

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014388.7(UTP25):​c.312A>C​(p.Glu104Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: UTP25 NM_014388.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.959
• Publications: 0 publications found

Genes affected

UTP25 (HGNC:28440): (UTP25 small subunit processome component) Enables RNA binding activity. Involved in several processes, including protein catabolic process; protein destabilization; and protein localization to nucleolus. Located in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.089821756).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014388.7. 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
	UTP25	NM_014388.7	MANE Select	c.312A>C	p.Glu104Asp	missense	Exon 3 of 12	NP_055203.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UTP25	ENST00000491415.7	TSL:1 MANE Select	c.312A>C	p.Glu104Asp	missense	Exon 3 of 12	ENSP00000419005.1	Q68CQ4
	UTP25	ENST00000852870.1		c.303A>C	p.Glu101Asp	missense	Exon 3 of 12	ENSP00000522929.1
	UTP25	ENST00000915424.1		c.312A>C	p.Glu104Asp	missense	Exon 3 of 12	ENSP00000585483.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	12
DANN	Uncertain	0.99
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-0.99	T
PhyloP100		0.96
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.013
Sift	Benign	0.17	T
Sift4G	Benign	0.35	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.021
Mutation Taster		=92/8	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-210004312;