5-73578821-G-T

Variant names:

• chr5-73578821-G-T
• rs146995054
• NM_032175.4:c.1115G>T

Variant summary

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

The NM_032175.4(UTP15):​c.1115G>T​(p.Arg372Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: UTP15 NM_032175.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.17

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.1115G>T	p.Arg372Leu	missense_variant	Exon 10 of 13	ENST00000296792.9	NP_115551.2
UTP15	NM_001284430.1	c.1058G>T	p.Arg353Leu	missense_variant	Exon 10 of 13		NP_001271359.1
UTP15	NM_001284431.1	c.545G>T	p.Arg182Leu	missense_variant	Exon 9 of 12		NP_001271360.1
UTP15	XM_011543680.3	c.1115G>T	p.Arg372Leu	missense_variant	Exon 10 of 13		XP_011541982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UTP15	ENST00000296792.9	c.1115G>T	p.Arg372Leu	missense_variant	Exon 10 of 13	1	NM_032175.4	ENSP00000296792.4
UTP15	ENST00000509005.5	c.1193G>T	p.Arg398Leu	missense_variant	Exon 9 of 12	2		ENSP00000421669.1
UTP15	ENST00000508491.1	c.1058G>T	p.Arg353Leu	missense_variant	Exon 10 of 13	2		ENSP00000424609.1
UTP15	ENST00000543251.5	c.545G>T	p.Arg182Leu	missense_variant	Exon 9 of 12	2		ENSP00000440796.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;.;.
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.50	T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.9	L;.;.
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.1	D;D;D
REVEL	Benign	0.17
Sift	Benign	0.033	D;D;D
Sift4G	Benign	0.13	T;T;T
Polyphen		0.12	B;.;.
Vest4		0.47
MutPred		0.67		Loss of MoRF binding (P = 0.0175);.;.;
MVP		0.25
MPC		0.48
ClinPred		0.97	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.22
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs146995054; hg19: chr5-72874646;