12-101291865-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_014503.3(UTP20):c.1015C>A(p.Pro339Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00779 in 1,613,108 control chromosomes in the GnomAD database, including 136 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (55 hom., cov: 33)
  • Exomes 𝑓: 0.0067 (81 hom.)
• Consequence: UTP20 NM_014503.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.313

Genes affected

UTP20 (HGNC:17897): (UTP20 small subunit processome component) UTP20 is a component of the U3 small nucleolar RNA (snoRNA) (SNORD3A; MIM 180710) protein complex (U3 snoRNP) and is involved in 18S rRNA processing (Wang et al., 2007 [PubMed 17498821]).[supplied by OMIM, Jun 2009]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0028953254).
• BP6: Variant 12-101291865-C-A is Benign according to our data. Variant chr12-101291865-C-A is described in ClinVar as [Benign]. Clinvar id is 782332.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0184 (2802/152288) while in subpopulation AFR AF= 0.0478 (1988/41556). AF 95% confidence interval is 0.0461. There are 55 homozygotes in gnomad4. There are 1339 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 51 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UTP20	NM_014503.3	c.1015C>A	p.Pro339Thr	missense_variant	9/62	ENST00000261637.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UTP20	ENST00000261637.5	c.1015C>A	p.Pro339Thr	missense_variant	9/62	1	NM_014503.3	P1

Frequencies

GnomAD3 genomes AF: 0.0182 AC: 2777 AN: 152170 Hom.: 51 Cov.: 33

Gnomad AFR AF: 0.0474

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0179

Gnomad ASJ AF: 0.0164

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00538

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00579

Gnomad OTH AF: 0.0248

GnomAD3 exomes AF: 0.00898 AC: 2248 AN: 250204 Hom.: 20 AF XY: 0.00839 AC XY: 1134 AN XY: 135194

Gnomad AFR exome AF: 0.0503

Gnomad AMR exome AF: 0.00918

Gnomad ASJ exome AF: 0.0173

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00523

Gnomad FIN exome AF: 0.000463

Gnomad NFE exome AF: 0.00626

Gnomad OTH exome AF: 0.0106

GnomAD4 exome AF: 0.00668 AC: 9762 AN: 1460820 Hom.: 81 Cov.: 31 AF XY: 0.00656 AC XY: 4763 AN XY: 726598

Gnomad4 AFR exome AF: 0.0491

Gnomad4 AMR exome AF: 0.0105

Gnomad4 ASJ exome AF: 0.0173

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00568

Gnomad4 FIN exome AF: 0.000449

Gnomad4 NFE exome AF: 0.00533

Gnomad4 OTH exome AF: 0.0105

GnomAD4 genome AF: 0.0184 AC: 2802 AN: 152288 Hom.: 55 Cov.: 33 AF XY: 0.0180 AC XY: 1339 AN XY: 74474

Gnomad4 AFR AF: 0.0478

Gnomad4 AMR AF: 0.0177

Gnomad4 ASJ AF: 0.0164

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00559

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.00582

Gnomad4 OTH AF: 0.0246

Alfa AF: 0.00806 Hom.: 19

Bravo AF: 0.0220

TwinsUK AF: 0.00593 AC: 22

ALSPAC AF: 0.00493 AC: 19

ESP6500AA AF: 0.0479 AC: 211

ESP6500EA AF: 0.00674 AC: 58

ExAC AF: 0.00931 AC: 1130

EpiCase AF: 0.00987

EpiControl AF: 0.00765

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 31, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.66
Cadd	Benign	3.1
Dann	Benign	0.042
DEOGEN2	Benign	0.0051	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.098	N
LIST_S2	Benign	0.19	T
MetaRNN	Benign	0.0029	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.6	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	2.4	N
REVEL	Benign	0.13
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.11
MVP		0.32
MPC		0.13
ClinPred		0.0026	T
GERP RS		3.1
Varity_R		0.025
gMVP		0.13

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

LitVar

Other links and lift over

dbSNP: rs75620118; hg19: chr12-101685643; COSMIC: COSV99079427; COSMIC: COSV99079427;