X-129911796-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000394422.8(UTP14A):​c.412G>A​(p.Ala138Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000265 in 1,208,916 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 11 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 0 hem., cov: 22)
Exomes 𝑓: 0.000026 ( 0 hom. 11 hem. )

Consequence

UTP14A
ENST00000394422.8 missense

Scores

1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.608
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.048381835).
BS2
High Hemizygotes in GnomAdExome4 at 11 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
UTP14ANM_006649.4 linkuse as main transcriptc.412G>A p.Ala138Thr missense_variant 6/15 ENST00000394422.8 NP_006640.2
LOC105373335XR_007068332.1 linkuse as main transcriptn.1774-2853C>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
UTP14AENST00000394422.8 linkuse as main transcriptc.412G>A p.Ala138Thr missense_variant 6/151 NM_006649.4 ENSP00000377944 P1Q9BVJ6-1
ENST00000432062.1 linkuse as main transcriptn.207-3243C>T intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.0000270
AC:
3
AN:
111063
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
AN XY:
33287
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000565
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000218
AC:
4
AN:
183331
Hom.:
0
AF XY:
0.0000295
AC XY:
2
AN XY:
67779
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000489
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000264
AC:
29
AN:
1097853
Hom.:
0
Cov.:
30
AF XY:
0.0000303
AC XY:
11
AN XY:
363227
show subpopulations
Gnomad4 AFR exome
AF:
0.0000379
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000370
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000297
Gnomad4 OTH exome
AF:
0.0000217
GnomAD4 genome
AF:
0.0000270
AC:
3
AN:
111063
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
AN XY:
33287
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000565
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000567
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000149
AC:
1
ExAC
AF:
0.0000330
AC:
4
EpiCase
AF:
0.00
EpiControl
AF:
0.000178

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 09, 2024The c.412G>A (p.A138T) alteration is located in exon 6 (coding exon 6) of the UTP14A gene. This alteration results from a G to A substitution at nucleotide position 412, causing the alanine (A) at amino acid position 138 to be replaced by a threonine (T). 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
0.071
BayesDel_addAF
Benign
-0.65
T
BayesDel_noAF
Benign
-1.1
CADD
Benign
8.4
DANN
Benign
0.95
DEOGEN2
Benign
0.0023
T
FATHMM_MKL
Benign
0.66
D
LIST_S2
Benign
0.41
T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.048
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.34
N
MutationTaster
Benign
1.0
D;N;N
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-0.32
N
REVEL
Benign
0.035
Sift
Benign
0.23
T
Sift4G
Uncertain
0.059
T
Polyphen
0.0040
B
Vest4
0.076
MVP
0.16
MPC
0.27
ClinPred
0.073
T
GERP RS
2.9
Varity_R
0.046
gMVP
0.17

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs150155910; hg19: chrX-129045772; COSMIC: COSV64086859; COSMIC: COSV64086859; API