dbSNP rs756428356: URM1:c.*1512C>A (chr9-128389413-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001135947.2(URM1):c.341C>A(p.Pro114His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000125 in 1,602,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P114L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

URM1
NM_001135947.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.15

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1754292).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
URM1	NM_030914.4 link	c.237+104C>A		intron_variant	Intron 4 of 4	ENST00000372853.9	NP_112176.1	Q9BTM9-1A0A024R8C7
URM1	NM_001135947.2 link	c.341C>A	p.Pro114His	missense_variant	Exon 4 of 4		NP_001129419.1	Q9BTM9-2
URM1	NM_001265582.1 link	c.*1512C>A		3_prime_UTR_variant	Exon 3 of 3		NP_001252511.1	Q9BTM9-3
URM1	NR_049743.2 link	n.285+104C>A		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
URM1	ENST00000372850.5 link	c.*1512C>A		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000361941.1	Q9BTM9-3
URM1	ENST00000372853.9 link	c.237+104C>A		intron_variant	Intron 4 of 4	1	NM_030914.4	ENSP00000361944.4	Q9BTM9-1
URM1	ENST00000483206.2 link	c.341C>A	p.Pro114His	missense_variant	Exon 4 of 4	2		ENSP00000501135.1	Q9BTM9-2
URM1	ENST00000470840.5 link	n.*86+104C>A		intron_variant	Intron 4 of 4	2		ENSP00000435186.1	Q5T4A9

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152166

Hom.:

Cov.:

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000445

AC:

AN:

224954

Hom.:

AF XY:

0.00

AC XY:

AN XY:

122130

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:

0.0000101

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1450698

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

720874

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:

9.03e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74342

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.077

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.37

M_CAP

Benign

0.0074

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.98

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.32

REVEL

Benign

0.20

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.99

Vest4

0.38

MutPred

0.094

Loss of glycosylation at P114 (P = 0.0132);

MVP

0.25

MPC

0.29

ClinPred

0.31

GERP RS

3.4

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over