12-101290197-A-G

Variant names:

• chr12-101290197-A-G
• rs1490242538
• NM_014503.3:c.658A>G

Variant summary

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

The NM_014503.3(UTP20):​c.658A>G​(p.Lys220Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,456,774 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: UTP20 NM_014503.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.12
• Publications: 0 publications found

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

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_014503.3. 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
	UTP20	NM_014503.3	MANE Select	c.658A>G	p.Lys220Glu	missense	Exon 7 of 62	NP_055318.2	O75691

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UTP20	ENST00000261637.5	TSL:1 MANE Select	c.658A>G	p.Lys220Glu	missense	Exon 7 of 62	ENSP00000261637.4	O75691
	UTP20	ENST00000551825.1	TSL:1	n.813A>G		non_coding_transcript_exon	Exon 7 of 8
	UTP20	ENST00000923497.1		c.658A>G	p.Lys220Glu	missense	Exon 7 of 62	ENSP00000593556.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000404 AC: 1 AN: 247612 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000303

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1456774 Hom.: 0 Cov.: 31 AF XY: 0.00000414 AC XY: 3 AN XY: 724532

African (AFR) AF: 0.00 AC: 0 AN: 33370

American (AMR) AF: 0.00 AC: 0 AN: 44038

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26074

East Asian (EAS) AF: 0.00 AC: 0 AN: 39544

South Asian (SAS) AF: 0.00 AC: 0 AN: 84894

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53328

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1109564

Other (OTH) AF: 0.00 AC: 0 AN: 60196

GnomAD4 genome Cov.: 32

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	Uncertain	0.56
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.47	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		9.1
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.30
Sift	Benign	0.43	T
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.75
MutPred		0.42		Loss of methylation at K220 (P = 0.0096)
MVP		0.83
MPC		0.64
ClinPred		0.78	D
GERP RS		5.8
Varity_R		0.33
gMVP		0.61
Mutation Taster		=49/51	disease causing

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: rs1490242538; hg19: chr12-101683975;