X-129919206-A-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_006649.4(UTP14A):ā€‹c.569A>Gā€‹(p.Asn190Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,209,435 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.0000090 ( 0 hom., 1 hem., cov: 23)
Exomes š‘“: 0.000013 ( 0 hom. 6 hem. )

Consequence

UTP14A
NM_006649.4 missense

Scores

2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.74
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 Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.13947007).
BS2
High Hemizygotes in GnomAdExome4 at 6 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
UTP14ANM_006649.4 linkc.569A>G p.Asn190Ser missense_variant 7/15 ENST00000394422.8 NP_006640.2 Q9BVJ6-1
UTP14ANM_001166221.2 linkc.413A>G p.Asn138Ser missense_variant 6/14 NP_001159693.1 Q9BVJ6-3
UTP14AXM_047441790.1 linkc.137A>G p.Asn46Ser missense_variant 3/11 XP_047297746.1
LOC105373335NR_188631.1 linkn.218+10552T>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
UTP14AENST00000394422.8 linkc.569A>G p.Asn190Ser missense_variant 7/151 NM_006649.4 ENSP00000377944.3 Q9BVJ6-1

Frequencies

GnomAD3 genomes
AF:
0.00000899
AC:
1
AN:
111239
Hom.:
0
Cov.:
23
AF XY:
0.0000299
AC XY:
1
AN XY:
33469
show subpopulations
Gnomad AFR
AF:
0.0000327
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000109
AC:
2
AN:
183512
Hom.:
0
AF XY:
0.0000147
AC XY:
1
AN XY:
67942
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000365
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:
0.0000122
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000127
AC:
14
AN:
1098196
Hom.:
0
Cov.:
31
AF XY:
0.0000165
AC XY:
6
AN XY:
363550
show subpopulations
Gnomad4 AFR exome
AF:
0.0000757
Gnomad4 AMR exome
AF:
0.0000284
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000131
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000899
AC:
1
AN:
111239
Hom.:
0
Cov.:
23
AF XY:
0.0000299
AC XY:
1
AN XY:
33469
show subpopulations
Gnomad4 AFR
AF:
0.0000327
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000264
ESP6500AA
AF:
0.000261
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000330
AC:
4
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

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 GeneticsJul 25, 2024The c.569A>G (p.N190S) alteration is located in exon 7 (coding exon 7) of the UTP14A gene. This alteration results from a A to G substitution at nucleotide position 569, causing the asparagine (N) at amino acid position 190 to be replaced by a serine (S). 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
0.066
BayesDel_addAF
Benign
-0.62
T
BayesDel_noAF
Benign
-1.0
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0021
.;T;T
FATHMM_MKL
Benign
0.43
N
LIST_S2
Uncertain
0.92
D;D;D
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.14
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.4
.;L;.
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-0.60
N;N;N
REVEL
Benign
0.14
Sift
Benign
0.26
T;T;T
Sift4G
Benign
1.0
T;T;T
Polyphen
0.75
.;P;.
Vest4
0.051
MVP
0.41
MPC
0.25
ClinPred
0.31
T
GERP RS
3.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
0.95
Varity_R
0.087
gMVP
0.12

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs377025264; hg19: chrX-129053182; API