12-101286495-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_014503.3(UTP20):c.501G>A(p.Met167Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 1,610,468 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M167T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0038 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00080 (2 hom.)
• Consequence: UTP20 NM_014503.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.22

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0038526356).
• BP6: Variant 12-101286495-G-A is Benign according to our data. Variant chr12-101286495-G-A is described in ClinVar as [Benign]. Clinvar id is 781260.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UTP20	NM_014503.3	c.501G>A	p.Met167Ile	missense_variant	5/62	ENST00000261637.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UTP20	ENST00000261637.5	c.501G>A	p.Met167Ile	missense_variant	5/62	1	NM_014503.3	P1
UTP20	ENST00000551825.1	n.656G>A		non_coding_transcript_exon_variant	5/8	1

Frequencies

GnomAD3 genomes AF: 0.00384 AC: 584 AN: 152140 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0124

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00152 AC: 379 AN: 249224 Hom.: 0 AF XY: 0.00126 AC XY: 170 AN XY: 134788

Gnomad AFR exome AF: 0.0128

Gnomad AMR exome AF: 0.00177

Gnomad ASJ exome AF: 0.00562

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000989

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000398

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.000798 AC: 1164 AN: 1458210 Hom.: 2 Cov.: 31 AF XY: 0.000706 AC XY: 512 AN XY: 725476

Gnomad4 AFR exome AF: 0.0150

Gnomad4 AMR exome AF: 0.00163

Gnomad4 ASJ exome AF: 0.00473

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000818

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.000315

Gnomad4 OTH exome AF: 0.00163

GnomAD4 genome AF: 0.00384 AC: 584 AN: 152258 Hom.: 4 Cov.: 32 AF XY: 0.00364 AC XY: 271 AN XY: 74444

Gnomad4 AFR AF: 0.0123

Gnomad4 AMR AF: 0.00157

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000323

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00116 Hom.: 0

Bravo AF: 0.00433

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.0120 AC: 53

ESP6500EA AF: 0.00105 AC: 9

ExAC AF: 0.00168 AC: 204

Asia WGS AF: 0.00144 AC: 5 AN: 3478

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

May 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.57
Cadd	Benign	19
Dann	Benign	0.91
DEOGEN2	Benign	0.0050	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.81	T
MetaRNN	Benign	0.0039	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.065	N
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.035
Sift	Benign	0.61	T
Sift4G	Benign	0.26	T
Polyphen		0.018	B
Vest4		0.19
MutPred		0.36		Gain of catalytic residue at S172 (P = 0);
MVP		0.33
MPC		0.13
ClinPred		0.015	T
GERP RS		4.4
Varity_R		0.10
gMVP		0.36

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: rs142220773; hg19: chr12-101680273;