Variant X-129906215-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_006649.4(UTP14A):c.5C>T(p.Thr2Ile) 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 1,208,303 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. 14/20 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: 𝑓 0.000027 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000026 ( 0 hom. 6 hem. )

Consequence

UTP14A
NM_006649.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.339

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]

UTP14A links:

ENSG00000235189 (HGNC:):

ENSG00000235189 links:

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=0.033082336).

BS2

High Hemizygotes in GnomAdExome4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UTP14A	NM_006649.4 linkuse as main transcript	c.5C>T	p.Thr2Ile	missense_variant	1/15	ENST00000394422.8	NP_006640.2	Q9BVJ6-1
UTP14A	NM_001166221.2 linkuse as main transcript	c.5C>T	p.Thr2Ile	missense_variant	1/14		NP_001159693.1	Q9BVJ6-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
UTP14A	ENST00000394422.8 linkuse as main transcript	c.5C>T	p.Thr2Ile	missense_variant	1/15	1	NM_006649.4	ENSP00000377944.3	Q9BVJ6-1
UTP14A	ENST00000425117.6 linkuse as main transcript	c.5C>T	p.Thr2Ile	missense_variant	1/14	2		ENSP00000388669.2	Q9BVJ6-3
ENSG00000235189	ENST00000432062.1 linkuse as main transcript	n.293+2252G>A		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000270

AC:

AN:

110985

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33171

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000287

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:

0.000143

AC:

AN:

181910

Hom.:

AF XY:

0.0000904

AC XY:

AN XY:

66406

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000879

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:

0.00

Gnomad OTH exome

AF:

0.000445

GnomAD4 exome

AF:

0.0000264

AC:

AN:

1097318

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

362690

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000768

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000664

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

AF:

0.0000270

AC:

AN:

110985

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33171

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000287

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

Alfa

AF:

0.0000845

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.000107

AC:

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 submitter

clinical testing

Ambry Genetics

Nov 09, 2024

The c.5C>T (p.T2I) alteration is located in exon 1 (coding exon 1) of the UTP14A gene. This alteration results from a C to T substitution at nucleotide position 5, causing the threonine (T) at amino acid position 2 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

Benign

0.15

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.99

CADD

Benign

7.0

DANN

Benign

0.96

DEOGEN2

Benign

0.0014

.;T

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.54

T;T

M_CAP

Benign

0.0048

MetaRNN

Benign

0.033

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.83

N;N

REVEL

Benign

0.026

Sift

Uncertain

0.010

D;D

Sift4G

Uncertain

0.017

D;D

Polyphen

0.10

.;B

Vest4

0.11

MutPred

0.26

Gain of helix (P = 0.0117);Gain of helix (P = 0.0117);

MVP

0.093

MPC

0.33

ClinPred

0.033

GERP RS

-2.7

Varity_R

0.049

gMVP

0.15

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over