chr5-73568301-A-G

Variant names:

• chr5-73568301-A-G
• rs139096826
• NM_032175.4:c.157A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001284431.1(UTP15):​c.-414A>G variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.000305 in 1,610,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00032 (0 hom.)
• Consequence: UTP15 NM_001284431.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.72
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.106333196).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001284431.1. 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.157A>G	p.Asn53Asp	missense	Exon 3 of 13	NP_115551.2	Q8TED0-1
	UTP15	NM_001284431.1		c.-414A>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 12	NP_001271360.1	Q8TED0-2
	UTP15	NM_001284430.1		c.100A>G	p.Asn34Asp	missense	Exon 3 of 13	NP_001271359.1	Q8TED0-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UTP15	ENST00000296792.9	TSL:1 MANE Select	c.157A>G	p.Asn53Asp	missense	Exon 3 of 13	ENSP00000296792.4	Q8TED0-1
	UTP15	ENST00000543251.5	TSL:2	c.-414A>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 12	ENSP00000440796.1	Q8TED0-2
	UTP15	ENST00000509005.5	TSL:2	c.235A>G	p.Asn79Asp	missense	Exon 2 of 12	ENSP00000421669.1	H0Y8P4

Frequencies

GnomAD3 genomes AF: 0.000184 AC: 28 AN: 152166 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000368

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000272 AC: 68 AN: 250276 AF XY: 0.000281

Gnomad AFR exome AF: 0.0000623

Gnomad AMR exome AF: 0.0000874

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000324

Gnomad NFE exome AF: 0.000450

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000318 AC: 464 AN: 1458628 Hom.: 0 Cov.: 31 AF XY: 0.000296 AC XY: 215 AN XY: 725442

African (AFR) AF: 0.00 AC: 0 AN: 33358

American (AMR) AF: 0.000112 AC: 5 AN: 44536

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39626

South Asian (SAS) AF: 0.000211 AC: 18 AN: 85488

European-Finnish (FIN) AF: 0.000563 AC: 30 AN: 53316

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4986

European-Non Finnish (NFE) AF: 0.000356 AC: 396 AN: 1111010

Other (OTH) AF: 0.000249 AC: 15 AN: 60210

GnomAD4 genome AF: 0.000184 AC: 28 AN: 152282 Hom.: 0 Cov.: 33 AF XY: 0.000161 AC XY: 12 AN XY: 74466

African (AFR) AF: 0.0000241 AC: 1 AN: 41548

American (AMR) AF: 0.0000653 AC: 1 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000368 AC: 25 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000334 Hom.: 0

Bravo AF: 0.000261

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000582 AC: 5

ExAC AF: 0.000288 AC: 35

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.045	T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		5.7
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.10
Sift	Benign	0.17	T
Sift4G	Uncertain	0.026	D
Polyphen		0.80	P
Vest4		0.64
MVP		0.39
MPC		0.54
ClinPred		0.051	T
GERP RS		4.4
Varity_R		0.24
gMVP		0.71
Mutation Taster		=236/64	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs139096826; hg19: chr5-72864126;