chrX-129920506-T-A

Position:

• chrX-129920506-T-A

Variant summary

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

The NM_006649.4(UTP14A):​c.802T>A​(p.Phe268Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: UTP14A NM_006649.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.65

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]

ENSG00000235189 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UTP14A	NM_006649.4	c.802T>A	p.Phe268Ile	missense_variant	9/15	ENST00000394422.8	NP_006640.2
UTP14A	NM_001166221.2	c.646T>A	p.Phe216Ile	missense_variant	8/14		NP_001159693.1
UTP14A	XM_047441790.1	c.370T>A	p.Phe124Ile	missense_variant	5/11		XP_047297746.1
LOC105373335	NR_188631.1	n.218+9252A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UTP14A	ENST00000394422.8	c.802T>A	p.Phe268Ile	missense_variant	9/15	1	NM_006649.4	ENSP00000377944.3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 22

Bravo AF: 0.00000756

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

Oct 26, 2022

The c.802T>A (p.F268I) alteration is located in exon 9 (coding exon 9) of the UTP14A gene. This alteration results from a T to A substitution at nucleotide position 802, causing the phenylalanine (F) at amino acid position 268 to be replaced by an isoleucine (I). 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	Uncertain	0.47
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.071	.;T;T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Uncertain	0.22	D
MetaRNN	Uncertain	0.55	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.0	.;M;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-4.1	D;D;D
REVEL	Uncertain	0.34
Sift	Uncertain	0.023	D;D;D
Sift4G	Benign	0.36	T;T;T
Polyphen		0.76	.;P;.
Vest4		0.55
MutPred		0.61		.;Loss of helix (P = 0.0558);.;
MVP		0.51
MPC		0.88
ClinPred		0.99	D
GERP RS		6.2
Varity_R		0.71
gMVP		0.27

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

LitVar

Other links and lift over

dbSNP: rs1383583388; hg19: chrX-129054482;