X-129907437-G-A

Position:

• chrX-129907437-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000394422.8(UTP14A):​c.97G>A​(p.Asp33Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: UTP14A ENST00000394422.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.45

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3267603).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UTP14A	NM_006649.4	c.97G>A	p.Asp33Asn	missense_variant	2/15	ENST00000394422.8	NP_006640.2
LOC105373335	XR_007068332.1	n.2250+1030C>T		intron_variant, non_coding_transcript_variant
UTP14A	NM_001166221.2	c.97G>A	p.Asp33Asn	missense_variant	2/14		NP_001159693.1
LOC105373335	XR_007068330.1	n.2329+951C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UTP14A	ENST00000394422.8	c.97G>A	p.Asp33Asn	missense_variant	2/15	1	NM_006649.4	ENSP00000377944	P1
	ENST00000432062.1	n.293+1030C>T		intron_variant, non_coding_transcript_variant		2
UTP14A	ENST00000425117.6	c.97G>A	p.Asp33Asn	missense_variant	2/14	2		ENSP00000388669
	ENST00000660217.1	n.1268C>T		non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 22

Bravo AF: 0.00000378

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

Aug 01, 2022

The c.97G>A (p.D33N) alteration is located in exon 2 (coding exon 2) of the UTP14A gene. This alteration results from a G to A substitution at nucleotide position 97, causing the aspartic acid (D) at amino acid position 33 to be replaced by an asparagine (N). 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	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.022	.;T
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.9	M;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Benign	0.19
Sift	Pathogenic	0.0	D;T
Sift4G	Benign	0.063	T;D
Polyphen		0.97	.;D
Vest4		0.52
MutPred		0.63		Loss of stability (P = 0.28);Loss of stability (P = 0.28);
MVP		0.70
MPC		0.93
ClinPred		1.0	D
GERP RS		4.9
Varity_R		0.44
gMVP		0.12

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: rs1929293112; hg19: chrX-129041413;