5-73570688-C-G

Variant names:

• chr5-73570688-C-G
• NM_032175.4:c.650C>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_032175.4(UTP15):​c.650C>G​(p.Ser217Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UTP15 NM_032175.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.775

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UTP15	NM_032175.4	c.650C>G	p.Ser217Cys	missense_variant	Exon 6 of 13	ENST00000296792.9	NP_115551.2
UTP15	NM_001284430.1	c.593C>G	p.Ser198Cys	missense_variant	Exon 6 of 13		NP_001271359.1
UTP15	NM_001284431.1	c.80C>G	p.Ser27Cys	missense_variant	Exon 5 of 12		NP_001271360.1
UTP15	XM_011543680.3	c.650C>G	p.Ser217Cys	missense_variant	Exon 6 of 13		XP_011541982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UTP15	ENST00000296792.9	c.650C>G	p.Ser217Cys	missense_variant	Exon 6 of 13	1	NM_032175.4	ENSP00000296792.4
UTP15	ENST00000509005.5	c.728C>G	p.Ser243Cys	missense_variant	Exon 5 of 12	2		ENSP00000421669.1
UTP15	ENST00000508491.1	c.593C>G	p.Ser198Cys	missense_variant	Exon 6 of 13	2		ENSP00000424609.1
UTP15	ENST00000543251.5	c.80C>G	p.Ser27Cys	missense_variant	Exon 5 of 12	2		ENSP00000440796.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.650C>G (p.S217C) alteration is located in exon 6 (coding exon 5) of the UTP15 gene. This alteration results from a C to G substitution at nucleotide position 650, causing the serine (S) at amino acid position 217 to be replaced by a cysteine (C). 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	0.22
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T;.;.
Eigen	Pathogenic	0.99
Eigen_PC	Pathogenic	0.96
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.78	D;D;D
MetaSVM	Uncertain	0.057	D
MutationAssessor	Pathogenic	3.2	M;.;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-4.0	D;D;D
REVEL	Uncertain	0.53
Sift	Uncertain	0.0050	D;D;D
Sift4G	Uncertain	0.0050	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.77
MutPred		0.49		Gain of catalytic residue at P216 (P = 0.0069);.;.;
MVP		0.46
MPC		1.1
ClinPred		0.99	D
GERP RS		6.2
Varity_R		0.82
gMVP		0.42

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-72866513;