5-73578820-C-T

Variant names:

• chr5-73578820-C-T
• rs140195152
• NM_032175.4:c.1114C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032175.4(UTP15):​c.1114C>T​(p.Arg372Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,608,540 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R372Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000024 (0 hom.)
• Consequence: UTP15 NM_032175.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.805
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35108748).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032175.4. 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
	UTP15	NM_032175.4	MANE Select	c.1114C>T	p.Arg372Trp	missense	Exon 10 of 13	NP_115551.2	Q8TED0-1
	UTP15	NM_001284430.1		c.1057C>T	p.Arg353Trp	missense	Exon 10 of 13	NP_001271359.1	Q8TED0-3
	UTP15	NM_001284431.1		c.544C>T	p.Arg182Trp	missense	Exon 9 of 12	NP_001271360.1	Q8TED0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UTP15	ENST00000296792.9	TSL:1 MANE Select	c.1114C>T	p.Arg372Trp	missense	Exon 10 of 13	ENSP00000296792.4	Q8TED0-1
	UTP15	ENST00000509005.5	TSL:2	c.1192C>T	p.Arg398Trp	missense	Exon 9 of 12	ENSP00000421669.1	H0Y8P4
	UTP15	ENST00000862251.1		c.1114C>T	p.Arg372Trp	missense	Exon 10 of 13	ENSP00000532310.1

Frequencies

GnomAD3 genomes AF: 0.0000266 AC: 4 AN: 150330 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

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: 0.0000449

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000199 AC: 5 AN: 251138 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

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: 0.0000441

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000240 AC: 35 AN: 1458210 Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12 AN XY: 725314

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26002

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39678

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86138

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53328

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.0000280 AC: 31 AN: 1109070

Other (OTH) AF: 0.0000333 AC: 2 AN: 60150

GnomAD4 genome AF: 0.0000266 AC: 4 AN: 150330 Hom.: 0 Cov.: 32 AF XY: 0.0000136 AC XY: 1 AN XY: 73496

African (AFR) AF: 0.0000242 AC: 1 AN: 41308

American (AMR) AF: 0.00 AC: 0 AN: 15018

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3420

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4790

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10566

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000449 AC: 3 AN: 66764

Other (OTH) AF: 0.00 AC: 0 AN: 2052

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.81
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.12
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.98	D
Vest4		0.39
MVP		0.21
MPC		0.76
ClinPred		0.77	D
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.29
gMVP		0.56
Mutation Taster		=86/14	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: rs140195152; hg19: chr5-72874645;