5-73570668-G-C

Variant names:

• chr5-73570668-G-C
• NM_032175.4:c.630G>C

Variant summary

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

The NM_032175.4(UTP15):​c.630G>C​(p.Glu210Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: UTP15 NM_032175.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.47

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, 0.762

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UTP15	NM_032175.4	c.630G>C	p.Glu210Asp	missense_variant	Exon 6 of 13	ENST00000296792.9	NP_115551.2
UTP15	NM_001284430.1	c.573G>C	p.Glu191Asp	missense_variant	Exon 6 of 13		NP_001271359.1
UTP15	NM_001284431.1	c.60G>C	p.Glu20Asp	missense_variant	Exon 5 of 12		NP_001271360.1
UTP15	XM_011543680.3	c.630G>C	p.Glu210Asp	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.630G>C	p.Glu210Asp	missense_variant	Exon 6 of 13	1	NM_032175.4	ENSP00000296792.4
UTP15	ENST00000509005.5	c.708G>C	p.Glu236Asp	missense_variant	Exon 5 of 12	2		ENSP00000421669.1
UTP15	ENST00000508491.1	c.573G>C	p.Glu191Asp	missense_variant	Exon 6 of 13	2		ENSP00000424609.1
UTP15	ENST00000543251.5	c.60G>C	p.Glu20Asp	missense_variant	Exon 5 of 12	2		ENSP00000440796.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461860 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 727230

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 03, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.630G>C (p.E210D) alteration is located in exon 6 (coding exon 5) of the UTP15 gene. This alteration results from a G to C substitution at nucleotide position 630, causing the glutamic acid (E) at amino acid position 210 to be replaced by an aspartic acid (D). 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	0.85
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.23
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T;.;.
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Benign	0.065	D
MetaRNN	Pathogenic	0.76	D;D;D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Uncertain	2.9	M;.;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-3.0	D;D;D
REVEL	Uncertain	0.33
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.80
MutPred		0.37		Loss of sheet (P = 0.0817);.;.;
MVP		0.82
MPC		1.0
ClinPred		0.98	D
GERP RS		4.2
Varity_R		0.82
gMVP		0.56

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: chr5-72866493;