NM_032175.4:c.895C>T

Variant names:

• chr5-73577856-C-T
• rs1561279602
• NM_032175.4:c.895C>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_032175.4(UTP15):​c.895C>T​(p.His299Tyr) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,424,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: UTP15 NM_032175.4 missense, splice_region
• Scores: Splicing: ADA: 0.9942
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.48
• Publications: 0 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

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.895C>T	p.His299Tyr	missense splice_region	Exon 9 of 13	NP_115551.2	Q8TED0-1
	UTP15	NM_001284430.1		c.838C>T	p.His280Tyr	missense splice_region	Exon 9 of 13	NP_001271359.1	Q8TED0-3
	UTP15	NM_001284431.1		c.325C>T	p.His109Tyr	missense splice_region	Exon 8 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.895C>T	p.His299Tyr	missense splice_region	Exon 9 of 13	ENSP00000296792.4	Q8TED0-1
	UTP15	ENST00000509005.5	TSL:2	c.973C>T	p.His325Tyr	missense splice_region	Exon 8 of 12	ENSP00000421669.1	H0Y8P4
	UTP15	ENST00000862251.1		c.895C>T	p.His299Tyr	missense splice_region	Exon 9 of 13	ENSP00000532310.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.02e-7 AC: 1 AN: 1424142 Hom.: 0 Cov.: 30 AF XY: 0.00000141 AC XY: 1 AN XY: 708452

African (AFR) AF: 0.00 AC: 0 AN: 30344

American (AMR) AF: 0.00 AC: 0 AN: 33740

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24824

East Asian (EAS) AF: 0.00 AC: 0 AN: 37478

South Asian (SAS) AF: 0.00 AC: 0 AN: 80332

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53030

Middle Eastern (MID) AF: 0.000177 AC: 1 AN: 5660

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1099954

Other (OTH) AF: 0.00 AC: 0 AN: 58780

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.085
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.060	T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		7.5
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.12
Sift	Benign	0.055	T
Sift4G	Uncertain	0.023	D
Polyphen		0.62	P
Vest4		0.39
MutPred		0.49		Loss of sheet (P = 0.0126)
MVP		0.21
MPC		0.49
ClinPred		0.80	D
GERP RS		5.4
Varity_R		0.093
gMVP		0.42
Mutation Taster		=59/41	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.99
dbscSNV1_RF	Pathogenic	0.84
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

Other links and lift over

dbSNP: rs1561279602; hg19: chr5-72873681;