5-73570668-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_032175.4(UTP15):​c.630G>C​(p.Glu210Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

UTP15
NM_032175.4 missense

Scores

7
9
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.47
Variant links:
Genes affected
UTP15 (HGNC:25758): (UTP15 small subunit processome component) Enables RNA binding activity. Involved in positive regulation of rRNA processing and positive regulation of transcription by RNA polymerase I. Located in endoplasmic reticulum and fibrillar center. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.762

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
UTP15NM_032175.4 linkc.630G>C p.Glu210Asp missense_variant Exon 6 of 13 ENST00000296792.9 NP_115551.2 Q8TED0-1
UTP15NM_001284430.1 linkc.573G>C p.Glu191Asp missense_variant Exon 6 of 13 NP_001271359.1 Q8TED0-3
UTP15NM_001284431.1 linkc.60G>C p.Glu20Asp missense_variant Exon 5 of 12 NP_001271360.1 Q8TED0-2
UTP15XM_011543680.3 linkc.630G>C p.Glu210Asp missense_variant Exon 6 of 13 XP_011541982.1 Q8TED0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
UTP15ENST00000296792.9 linkc.630G>C p.Glu210Asp missense_variant Exon 6 of 13 1 NM_032175.4 ENSP00000296792.4 Q8TED0-1
UTP15ENST00000509005.5 linkc.708G>C p.Glu236Asp missense_variant Exon 5 of 12 2 ENSP00000421669.1 H0Y8P4
UTP15ENST00000508491.1 linkc.573G>C p.Glu191Asp missense_variant Exon 6 of 13 2 ENSP00000424609.1 Q8TED0-3
UTP15ENST00000543251.5 linkc.60G>C p.Glu20Asp missense_variant Exon 5 of 12 2 ENSP00000440796.1 Q8TED0-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000410
AC:
6
AN:
1461860
Hom.:
0
Cov.:
31
AF XY:
0.00000550
AC XY:
4
AN XY:
727230
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 03, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.630G>C (p.E210D) alteration is located in exon 6 (coding exon 5) of the UTP15 gene. This alteration results from a G to C substitution at nucleotide position 630, causing the glutamic acid (E) at amino acid position 210 to be replaced by an aspartic acid (D). 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
Pathogenic
0.85
BayesDel_addAF
Pathogenic
0.33
D
BayesDel_noAF
Pathogenic
0.23
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.22
T;.;.
Eigen
Uncertain
0.39
Eigen_PC
Uncertain
0.41
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.92
D;D;D
M_CAP
Benign
0.065
D
MetaRNN
Pathogenic
0.76
D;D;D
MetaSVM
Uncertain
-0.22
T
MutationAssessor
Uncertain
2.9
M;.;.
PrimateAI
Uncertain
0.68
T
PROVEAN
Uncertain
-3.0
D;D;D
REVEL
Uncertain
0.33
Sift
Pathogenic
0.0
D;D;D
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
1.0
D;.;.
Vest4
0.80
MutPred
0.37
Loss of sheet (P = 0.0817);.;.;
MVP
0.82
MPC
1.0
ClinPred
0.98
D
GERP RS
4.2
Varity_R
0.82
gMVP
0.56

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: chr5-72866493; API