NM_032175.4:c.944T>C

Variant names:

• chr5-73577905-T-C
• rs1748148864
• NM_032175.4:c.944T>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032175.4(UTP15):​c.944T>C​(p.Val315Ala) 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: 7.58

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.944T>C	p.Val315Ala	missense_variant	Exon 9 of 13	ENST00000296792.9	NP_115551.2
UTP15	NM_001284430.1	c.887T>C	p.Val296Ala	missense_variant	Exon 9 of 13		NP_001271359.1
UTP15	NM_001284431.1	c.374T>C	p.Val125Ala	missense_variant	Exon 8 of 12		NP_001271360.1
UTP15	XM_011543680.3	c.944T>C	p.Val315Ala	missense_variant	Exon 9 of 13		XP_011541982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UTP15	ENST00000296792.9	c.944T>C	p.Val315Ala	missense_variant	Exon 9 of 13	1	NM_032175.4	ENSP00000296792.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.944T>C (p.V315A) alteration is located in exon 9 (coding exon 8) of the UTP15 gene. This alteration results from a T to C substitution at nucleotide position 944, causing the valine (V) at amino acid position 315 to be replaced by an alanine (A). 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	Pathogenic	0.75
BayesDel_addAF	Uncertain	0.078	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T;.;.
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.86	D;D;D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.68	D;D;D
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.0	M;.;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-3.9	D;D;D
REVEL	Benign	0.22
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		0.43	B;.;.
Vest4		0.74
MutPred		0.66		Gain of disorder (P = 0.0409);.;.;
MVP		0.27
MPC		0.77
ClinPred		0.97	D
GERP RS		5.4
Varity_R		0.47
gMVP		0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs1748148864; hg19: chr5-72873730;