chrX-47658872-C-T

Variant names:

• chrX-47658872-C-T
• rs750539582
• NM_153477.3:c.92G>A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4 BS2

The NM_153477.3(UXT):​c.92G>A​(p.Arg31His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000759 in 1,053,722 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 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: 24)
  • Exomes 𝑓: 0.0000076 (0 hom. 6 hem.)
• Consequence: UXT NM_153477.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.97

Genes affected

UXT (HGNC:12641): (ubiquitously expressed prefoldin like chaperone) The protein encoded by this gene functions as a cofactor that modulates androgen receptor-dependent transcription, and also plays a critical role in tumor necrosis factor-induced apoptosis. Expression of this gene may play a role in tumorigenesis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

UXT-AS1 (HGNC:49239): (UXT antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3521936).
• BS2: High Hemizygotes in GnomAdExome4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UXT	NM_153477.3	c.92G>A	p.Arg31His	missense_variant	Exon 1 of 6	ENST00000335890.3	NP_705582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UXT	ENST00000335890.3	c.92G>A	p.Arg31His	missense_variant	Exon 1 of 6	1	NM_153477.3	ENSP00000337393.2
UXT	ENST00000333119.8	c.56G>A	p.Arg19His	missense_variant	Exon 2 of 7	1		ENSP00000327797.3

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD3 exomes AF: 0.0000279 AC: 4 AN: 143296 Hom.: 0 AF XY: 0.0000677 AC XY: 3 AN XY: 44308

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000319

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000759 AC: 8 AN: 1053722 Hom.: 0 Cov.: 31 AF XY: 0.0000177 AC XY: 6 AN XY: 339066

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000269

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

ExAC AF: 0.0000166 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.92G>A (p.R31H) alteration is located in exon 1 (coding exon 1) of the UXT gene. This alteration results from a G to A substitution at nucleotide position 92, causing the arginine (R) at amino acid position 31 to be replaced by a histidine (H). 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	0.14
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.18	T;.
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.84	T;T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	2.0	M;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.14
Sift	Uncertain	0.020	D;D
Sift4G	Uncertain	0.030	D;D
Polyphen		0.99	D;.
Vest4		0.56
MutPred		0.36		Loss of MoRF binding (P = 0.0382);.;
MVP		0.37
MPC		1.6
ClinPred		0.37	T
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.37

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: rs750539582; hg19: chrX-47518271;