5-73567360-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UTP15	NM_032175.4	c.16C>A	p.Pro6Thr	missense_variant	Exon 2 of 13	ENST00000296792.9	NP_115551.2
UTP15	NM_001284430.1	c.16C>A	p.Pro6Thr	missense_variant	Exon 2 of 13		NP_001271359.1
UTP15	XM_011543680.3	c.16C>A	p.Pro6Thr	missense_variant	Exon 2 of 13		XP_011541982.1
UTP15	NM_001284431.1	c.-480-875C>A		intron_variant	Intron 1 of 11		NP_001271360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UTP15	ENST00000296792.9	c.16C>A	p.Pro6Thr	missense_variant	Exon 2 of 13	1	NM_032175.4	ENSP00000296792.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 03, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.16C>A (p.P6T) alteration is located in exon 2 (coding exon 1) of the UTP15 gene. This alteration results from a C to A substitution at nucleotide position 16, causing the proline (P) at amino acid position 6 to be replaced by a threonine (T). 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	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;T;.;T
M_CAP	Benign	0.063	D
MetaRNN	Uncertain	0.74	D;D;D;D
MetaSVM	Benign	-0.55	T
MutationAssessor	Pathogenic	2.9	.;M;.;M
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-2.9	D;N;D;N
REVEL	Uncertain	0.32
Sift	Uncertain	0.027	D;T;.;T
Sift4G	Uncertain	0.017	D;D;.;D
Polyphen		0.73	.;P;.;.
Vest4		0.42, 0.64
MutPred		0.66		Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1246567378; hg19: chr5-72863185;