Variant 19-30005367-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003796.3(URI1):c.374G>A(p.Arg125Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000203 in 1,575,848 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000019 ( 1 hom. )

Consequence

URI1
NM_003796.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.65

Variant links:

Genes affected

URI1 (HGNC:13236): (URI1 prefoldin like chaperone) This gene encodes member of the prefoldin family of molecular chaperones. The encoded protein functions as a scaffolding protein and plays roles in ubiquitination and transcription, in part though interactions with the RNA polymerase II subunit RPB5. This gene may play a role in multiple malignancies including ovarian cancer and hepatocellular carcinoma. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 22. [provided by RefSeq, Nov 2011]

URI1 links:

URI1 (HGNC:):

URI1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15273306).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
URI1	NM_003796.3 linkuse as main transcript	c.374G>A	p.Arg125Lys	missense_variant	5/11	ENST00000392271.6	NP_003787.2	O94763-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
URI1	ENST00000392271.6 linkuse as main transcript	c.374G>A	p.Arg125Lys	missense_variant	5/11	1	NM_003796.3	ENSP00000376097.2		O94763-1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

151906

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

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:

0.0000442

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000214

AC:

AN:

233176

Hom.:

AF XY:

0.0000158

AC XY:

AN XY:

126288

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000996

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:

0.00000928

Gnomad OTH exome

AF:

0.000178

GnomAD4 exome

AF:

0.0000190

AC:

AN:

1423824

Hom.:

Cov.:

AF XY:

0.0000212

AC XY:

AN XY:

709144

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000150

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:

0.0000175

Gnomad4 OTH exome

AF:

0.0000340

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152024

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000442

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000283

Hom.:

Bravo

AF:

0.0000756

ExAC

AF:

0.0000247

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

Feb 17, 2023

The c.374G>A (p.R125K) alteration is located in exon 5 (coding exon 5) of the URI1 gene. This alteration results from a G to A substitution at nucleotide position 374, causing the arginine (R) at amino acid position 125 to be replaced by a lysine (K). 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

0.11

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0084

.;T;T;.

Eigen

Benign

0.12

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.66

T;T;T;T

M_CAP

Benign

0.038

MetaRNN

Benign

0.15

T;T;T;T

MetaSVM

Benign

-0.31

MutationAssessor

Benign

0.85

.;.;L;.

PrimateAI

Uncertain

0.54

REVEL

Benign

0.10

Sift4G

Benign

0.36

T;T;T;T

Polyphen

0.53

.;.;P;.

Vest4

0.20

MutPred

0.39

.;.;Gain of methylation at R125 (P = 0.0167);.;

MVP

0.78

ClinPred

0.29

GERP RS

4.5

Varity_R

0.21

gMVP

0.44

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