12-101286352-A-G

Variant names:

• chr12-101286352-A-G
• rs781676133
• NM_014503.3:c.358A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014503.3(UTP20):​c.358A>G​(p.Met120Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 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. M120L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: UTP20 NM_014503.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.45
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10125914).

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.358A>G	p.Met120Val	missense	Exon 5 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.358A>G	p.Met120Val	missense	Exon 5 of 62	ENSP00000261637.4	O75691
	UTP20	ENST00000551825.1	TSL:1	n.513A>G		non_coding_transcript_exon	Exon 5 of 8
	UTP20	ENST00000923497.1		c.358A>G	p.Met120Val	missense	Exon 5 of 62	ENSP00000593556.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.0044	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.41	N
PhyloP100		4.4
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.074
Sift	Benign	0.16	T
Sift4G	Benign	0.31	T
Polyphen		0.0030	B
Vest4		0.13
MutPred		0.35		Gain of catalytic residue at M120 (P = 0.0307)
MVP		0.34
MPC		0.12
ClinPred		0.67	D
GERP RS		5.5
Varity_R		0.076
gMVP		0.15
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs781676133; hg19: chr12-101680130;