17-31880587-T-C

Variant names:

• chr17-31880587-T-C
• rs1910769516
• NM_018428.3:c.953A>G

Variant summary

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

The NM_018428.3(UTP6):​c.953A>G​(p.Lys318Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: UTP6 NM_018428.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.792

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

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=0.068226546).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UTP6	NM_018428.3	c.953A>G	p.Lys318Arg	missense_variant	Exon 11 of 19	ENST00000261708.9	NP_060898.2
UTP6	XM_011524997.4	c.953A>G	p.Lys318Arg	missense_variant	Exon 11 of 18		XP_011523299.1
UTP6	XM_047436390.1	c.590A>G	p.Lys197Arg	missense_variant	Exon 9 of 17		XP_047292346.1
UTP6	XM_047436391.1	c.953A>G	p.Lys318Arg	missense_variant	Exon 11 of 13		XP_047292347.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UTP6	ENST00000261708.9	c.953A>G	p.Lys318Arg	missense_variant	Exon 11 of 19	1	NM_018428.3	ENSP00000261708.4
UTP6	ENST00000477128.5	n.1318A>G		non_coding_transcript_exon_variant	Exon 4 of 12	2
UTP6	ENST00000583408.5	n.1034A>G		non_coding_transcript_exon_variant	Exon 11 of 11	2
ENSG00000263990	ENST00000583236.1	n.394-5985T>C		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461870 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727238

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 10, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.953A>G (p.K318R) alteration is located in exon 11 (coding exon 11) of the UTP6 gene. This alteration results from a A to G substitution at nucleotide position 953, causing the lysine (K) at amino acid position 318 to be replaced by an arginine (R). 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	0.069
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.0086	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.017
Sift	Benign	0.16	T
Sift4G	Benign	0.090	T
Polyphen		0.011	B
Vest4		0.12
MutPred		0.37		Loss of methylation at K318 (P = 0.0056);
MVP		0.34
MPC		0.075
ClinPred		0.077	T
GERP RS		1.8
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.0
Varity_R		0.036
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1910769516; hg19: chr17-30207606;