X-129921272-G-A

Position:

• chrX-129921272-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_006649.4(UTP14A):​c.1033G>A​(p.Glu345Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00002 in 1,098,208 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.000020 (0 hom. 5 hem.)
• Consequence: UTP14A NM_006649.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.89

Genes affected

UTP14A (HGNC:10665): (UTP14A small subunit processome component) This gene encodes a member of the uridine triphosphate 14 family. As an essential component of a large ribonucleoprotein complex bound to the U3 small nucleolar RNA, the encoded protein is involved in ribosome biogenesis and 18S rRNA synthesis. An autosomal retrotransposed copy of this X-linked gene exists on chromosome 13. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Oct 2009]

UTP14A (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2362304).
• BS2: High Hemizygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UTP14A	NM_006649.4	c.1033G>A	p.Glu345Lys	missense_variant	11/15	ENST00000394422.8	NP_006640.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UTP14A	ENST00000394422.8	c.1033G>A	p.Glu345Lys	missense_variant	11/15	1	NM_006649.4	ENSP00000377944.3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.0000200 AC: 22 AN: 1098208 Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 5 AN XY: 363562

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: 0.0000185

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000237

Gnomad4 OTH exome AF: 0.0000217

GnomAD4 genome Cov.: 22

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

Dec 28, 2022

The c.1033G>A (p.E345K) alteration is located in exon 11 (coding exon 11) of the UTP14A gene. This alteration results from a G to A substitution at nucleotide position 1033, causing the glutamic acid (E) at amino acid position 345 to be replaced by a lysine (K). 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	0.11
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.0094	.;T;T
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-0.76	T
MutationAssessor	Pathogenic	3.0	.;M;.
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.5	N;N;D
REVEL	Benign	0.12
Sift	Uncertain	0.0070	D;D;D
Sift4G	Benign	0.22	T;T;T
Polyphen		0.98	.;D;.
Vest4		0.17
MutPred		0.48		.;Gain of ubiquitination at E345 (P = 0.0016);.;
MVP		0.34
MPC		0.97
ClinPred		0.94	D
GERP RS		3.7
Varity_R		0.39
gMVP		0.22

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-129055248;