5-73576974-A-G

Variant names:

• chr5-73576974-A-G
• rs112991877
• NM_032175.4:c.832A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032175.4(UTP15):​c.832A>G​(p.Thr278Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000373 in 1,608,382 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: UTP15 NM_032175.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.25
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06208843).

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.832A>G	p.Thr278Ala	missense	Exon 8 of 13	NP_115551.2	Q8TED0-1
	UTP15	NM_001284430.1		c.775A>G	p.Thr259Ala	missense	Exon 8 of 13	NP_001271359.1	Q8TED0-3
	UTP15	NM_001284431.1		c.262A>G	p.Thr88Ala	missense	Exon 7 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.832A>G	p.Thr278Ala	missense	Exon 8 of 13	ENSP00000296792.4	Q8TED0-1
	UTP15	ENST00000509005.5	TSL:2	c.910A>G	p.Thr304Ala	missense	Exon 7 of 12	ENSP00000421669.1	H0Y8P4
	UTP15	ENST00000862251.1		c.832A>G	p.Thr278Ala	missense	Exon 8 of 13	ENSP00000532310.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152260 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1456004 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 724072

African (AFR) AF: 0.0000302 AC: 1 AN: 33132

American (AMR) AF: 0.00 AC: 0 AN: 43156

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25938

East Asian (EAS) AF: 0.00 AC: 0 AN: 39600

South Asian (SAS) AF: 0.00 AC: 0 AN: 84422

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53334

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110494

Other (OTH) AF: 0.0000166 AC: 1 AN: 60190

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152378 Hom.: 0 Cov.: 32 AF XY: 0.0000268 AC XY: 2 AN XY: 74520

African (AFR) AF: 0.0000481 AC: 2 AN: 41596

American (AMR) AF: 0.00 AC: 0 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	0.066
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	6.6
DANN	Benign	0.48
DEOGEN2	Benign	0.020	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.3
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.045
Sift	Benign	0.59	T
Sift4G	Benign	0.88	T
Polyphen		0.0010	B
Vest4		0.21
MutPred		0.29		Gain of MoRF binding (P = 0.0995)
MVP		0.38
MPC		0.32
ClinPred		0.031	T
GERP RS		-2.1
Varity_R		0.020
gMVP		0.27
Mutation Taster		=85/15	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

Other links and lift over

dbSNP: rs112991877; hg19: chr5-72872799;