Variant X-129920702-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The ENST00000394422.8(UTP14A):c.904A>C(p.Ser302Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000323 in 1,207,993 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: 𝑓 0.0000091 ( 0 hom., 0 hem., cov: 21)

Exomes 𝑓: 0.000035 ( 0 hom. 6 hem. )

Consequence

UTP14A
ENST00000394422.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.93

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.38862008).

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.904A>C	p.Ser302Arg	missense_variant	10/15	ENST00000394422.8	NP_006640.2
LOC105373335	XR_007068332.1 linkuse as main transcript	n.1773+9056T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UTP14A	ENST00000394422.8 linkuse as main transcript	c.904A>C	p.Ser302Arg	missense_variant	10/15	1	NM_006649.4	ENSP00000377944	P1	Q9BVJ6-1
	ENST00000432062.1 linkuse as main transcript	n.206+9056T>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00000911

AC:

AN:

109741

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32011

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:

0.0000190

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000346

AC:

AN:

1098252

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

363606

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.0000568

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:

0.0000416

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000911

AC:

AN:

109741

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32011

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:

0.0000190

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

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

Sep 06, 2022

The c.904A>C (p.S302R) alteration is located in exon 10 (coding exon 10) of the UTP14A gene. This alteration results from a A to C substitution at nucleotide position 904, causing the serine (S) at amino acid position 302 to be replaced by an arginine (R). 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

Pathogenic

0.75

BayesDel_addAF

Uncertain

0.025

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0096

.;T;T

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.39

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Pathogenic

3.1

.;M;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-2.5

N;N;D

REVEL

Benign

0.27

Sift

Uncertain

0.0040

D;D;D

Sift4G

Benign

0.077

T;D;T

Polyphen

0.97

.;D;.

Vest4

0.45

MutPred

0.34

.;Loss of phosphorylation at S302 (P = 0.0408);.;

MVP

0.35

MPC

0.59

ClinPred

0.97

GERP RS

6.1

Varity_R

0.76

gMVP

0.28

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