17-31873684-C-T

Variant names:

• chr17-31873684-C-T
• rs1435615949
• NM_018428.3:c.1375G>A

Variant summary

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

The NM_018428.3(UTP6):​c.1375G>A​(p.Ala459Thr) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: UTP6 NM_018428.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.52
• Publications: 0 publications found

Genes affected

UTP6 (HGNC:18279): (UTP6 small subunit processome component) Predicted to enable snoRNA binding activity. Predicted to be involved in maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA). Located in chromosome and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000263990 (HGNC:):

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=0.11972001).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018428.3. 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
	UTP6	NM_018428.3	MANE Select	c.1375G>A	p.Ala459Thr	missense	Exon 15 of 19	NP_060898.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UTP6	ENST00000261708.9	TSL:1 MANE Select	c.1375G>A	p.Ala459Thr	missense	Exon 15 of 19	ENSP00000261708.4	Q9NYH9
	UTP6	ENST00000899559.1		c.1372G>A	p.Ala458Thr	missense	Exon 15 of 19	ENSP00000569618.1
	UTP6	ENST00000940126.1		c.1372G>A	p.Ala458Thr	missense	Exon 15 of 19	ENSP00000610185.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	Benign	0.077
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0098	T
Eigen	Benign	-0.040
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		1.5
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.11
Sift	Benign	0.21	T
Sift4G	Benign	0.14	T
Polyphen		0.011	B
Vest4		0.11
MutPred		0.47		Gain of ubiquitination at K463 (P = 0.1162)
MVP		0.52
MPC		0.091
ClinPred		0.74	D
GERP RS		5.1
PromoterAI		0.0046	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.055
gMVP		0.18

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

Other links and lift over

dbSNP: rs1435615949; hg19: chr17-30200703;