chr5-73567360-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_032175.4(UTP15):​c.16C>T​(p.Pro6Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,454,382 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P6T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: UTP15 NM_032175.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.25
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032175.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UTP15	NM_032175.4	MANE Select	c.16C>T	p.Pro6Ser	missense	Exon 2 of 13	NP_115551.2	Q8TED0-1
	UTP15	NM_001284430.1		c.16C>T	p.Pro6Ser	missense	Exon 2 of 13	NP_001271359.1	Q8TED0-3
	UTP15	NM_001284431.1		c.-480-875C>T		intron	N/A	NP_001271360.1	Q8TED0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UTP15	ENST00000296792.9	TSL:1 MANE Select	c.16C>T	p.Pro6Ser	missense	Exon 2 of 13	ENSP00000296792.4	Q8TED0-1
	UTP15	ENST00000862251.1		c.16C>T	p.Pro6Ser	missense	Exon 2 of 13	ENSP00000532310.1
	UTP15	ENST00000862252.1		c.16C>T	p.Pro6Ser	missense	Exon 3 of 14	ENSP00000532311.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1454382 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 723484

African (AFR) AF: 0.00 AC: 0 AN: 33140

American (AMR) AF: 0.00 AC: 0 AN: 43812

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25958

East Asian (EAS) AF: 0.00 AC: 0 AN: 39166

South Asian (SAS) AF: 0.00 AC: 0 AN: 85072

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53260

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1108162

Other (OTH) AF: 0.00 AC: 0 AN: 60060

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.059	T
Eigen	Benign	0.095
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		7.2
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.23
Sift	Benign	0.15	T
Sift4G	Benign	0.11	T
Polyphen		0.067	B
Vest4		0.39
MutPred		0.55		Gain of sheet (P = 0.0477)
MVP		0.47
MPC		0.69
ClinPred		0.94	D
GERP RS		5.0
Varity_R		0.23
gMVP		0.69
Mutation Taster		=23/77	disease causing

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

Other links and lift over

dbSNP: rs1246567378; hg19: chr5-72863185;