rs1246567378

Variant names:

• chr5-73567360-C-A
• rs1246567378
• NM_032175.4:c.16C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-73567360-C-A
• chr5-73567360-C-T

Variant summary

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

The NM_032175.4(UTP15):​c.16C>A​(p.Pro6Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: UTP15 NM_032175.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.25
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.16C>A	p.Pro6Thr	missense	Exon 2 of 13	NP_115551.2	Q8TED0-1
	UTP15	NM_001284430.1		c.16C>A	p.Pro6Thr	missense	Exon 2 of 13	NP_001271359.1	Q8TED0-3
	UTP15	NM_001284431.1		c.-480-875C>A		intron	N/A	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.16C>A	p.Pro6Thr	missense	Exon 2 of 13	ENSP00000296792.4	Q8TED0-1
	UTP15	ENST00000862251.1		c.16C>A	p.Pro6Thr	missense	Exon 2 of 13	ENSP00000532310.1
	UTP15	ENST00000862252.1		c.16C>A	p.Pro6Thr	missense	Exon 3 of 14	ENSP00000532311.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 246316 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

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	0.26
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.063	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.55	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		7.2
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.027	D
Sift4G	Uncertain	0.017	D
Polyphen		0.73	P
Vest4		0.42
MutPred		0.66		Gain of sheet (P = 0.0344)
MVP		0.48
MPC		1.0
ClinPred		0.98	D
GERP RS		5.0
Varity_R		0.29
gMVP		0.70
Mutation Taster		=19/81	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1246567378; hg19: chr5-72863185;