12-101290832-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014503.3(UTP20):c.835T>A(p.Ser279Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UTP20 NM_014503.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.37

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15111747).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UTP20	NM_014503.3	c.835T>A	p.Ser279Thr	missense_variant	8/62	ENST00000261637.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UTP20	ENST00000261637.5	c.835T>A	p.Ser279Thr	missense_variant	8/62	1	NM_014503.3	P1
UTP20	ENST00000551825.1	n.990T>A		non_coding_transcript_exon_variant	8/8	1
UTP20	ENST00000551998.1	n.472T>A		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 06, 2021

The c.835T>A (p.S279T) alteration is located in exon 8 (coding exon 8) of the UTP20 gene. This alteration results from a T to A substitution at nucleotide position 835, causing the serine (S) at amino acid position 279 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
Cadd	Benign	18
Dann	Benign	0.79
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.069
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.7	L
MutationTaster	Benign	0.98	D
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.092
Sift	Benign	0.30	T
Sift4G	Benign	0.18	T
Polyphen		0.084	B
Vest4		0.31
MutPred		0.39		Gain of catalytic residue at S282 (P = 3e-04);
MVP		0.53
MPC		0.16
ClinPred		0.24	T
GERP RS		4.2
Varity_R		0.057
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-101684610;