Genetic Variant URM1:p.Pro54Ser (chr9-128387869-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_030914.4(URM1):c.160C>T(p.Pro54Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000103 in 1,461,826 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

URM1
NM_030914.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.04

Variant links:

Genes affected

URM1 (HGNC:28378): (ubiquitin related modifier 1) Enables sulfur carrier activity. Involved in tRNA thio-modification and tRNA wobble uridine modification. Predicted to be located in cytosol. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

URM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
URM1	NM_030914.4 link	c.160C>T	p.Pro54Ser	missense_variant	Exon 3 of 5	ENST00000372853.9	NP_112176.1	Q9BTM9-1A0A024R8C7
URM1	NM_001135947.2 link	c.160C>T	p.Pro54Ser	missense_variant	Exon 3 of 4		NP_001129419.1	Q9BTM9-2
URM1	NM_001265582.1 link	c.160C>T	p.Pro54Ser	missense_variant	Exon 3 of 3		NP_001252511.1	Q9BTM9-3
URM1	NR_049743.2 link	n.208C>T		non_coding_transcript_exon_variant	Exon 3 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
URM1	ENST00000372853.9 link	c.160C>T	p.Pro54Ser	missense_variant	Exon 3 of 5	1	NM_030914.4	ENSP00000361944.4		Q9BTM9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251462

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135912

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:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1461826

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000135

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000450

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.160C>T (p.P54S) alteration is located in exon 3 (coding exon 3) of the URM1 gene. This alteration results from a C to T substitution at nucleotide position 160, causing the proline (P) at amino acid position 54 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

0.26

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

T;.;.

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

D;D;D

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.44

T;T;T

MetaSVM

Benign

-0.39

MutationAssessor

Uncertain

2.3

M;M;M

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-5.7

D;D;D

REVEL

Uncertain

0.41

Sift

Benign

0.038

D;D;D

Sift4G

Benign

0.12

T;D;T

Polyphen

0.14

B;.;B

Vest4

0.71

MutPred

0.53

Loss of glycosylation at P54 (P = 0.0394);Loss of glycosylation at P54 (P = 0.0394);Loss of glycosylation at P54 (P = 0.0394);

MVP

0.25

MPC

0.35

ClinPred

0.95

GERP RS

5.7

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.38

gMVP

0.56

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.

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