9-128389413-C-G

Variant names:

• chr9-128389413-C-G
• rs756428356
• ENST00000372850.5:c.*1512C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001135947.2(URM1):​c.341C>G​(p.Pro114Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,450,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 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: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: URM1 NM_001135947.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.15
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1622828).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135947.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	URM1	NM_030914.4	MANE Select	c.237+104C>G		intron	N/A	NP_112176.1	Q9BTM9-1
	URM1	NM_001135947.2		c.341C>G	p.Pro114Arg	missense	Exon 4 of 4	NP_001129419.1	Q9BTM9-2
	URM1	NM_001265582.1		c.*1512C>G		3_prime_UTR	Exon 3 of 3	NP_001252511.1	Q9BTM9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	URM1	ENST00000372850.5	TSL:1	c.*1512C>G		3_prime_UTR	Exon 3 of 3	ENSP00000361941.1	Q9BTM9-3
	URM1	ENST00000372853.9	TSL:1 MANE Select	c.237+104C>G		intron	N/A	ENSP00000361944.4	Q9BTM9-1
	URM1	ENST00000483206.2	TSL:2	c.341C>G	p.Pro114Arg	missense	Exon 4 of 4	ENSP00000501135.1	Q9BTM9-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000445 AC: 1 AN: 224954 AF XY: 0.00000819

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000101

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1450698 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 720874

African (AFR) AF: 0.00 AC: 0 AN: 33248

American (AMR) AF: 0.00 AC: 0 AN: 42382

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25786

East Asian (EAS) AF: 0.00 AC: 0 AN: 39318

South Asian (SAS) AF: 0.00 AC: 0 AN: 85108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52302

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1106826

Other (OTH) AF: 0.00 AC: 0 AN: 59974

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	13
DANN	Uncertain	1.0
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
PhyloP100		2.1
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.099
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.95	P
Vest4		0.39
MutPred		0.12		Loss of glycosylation at P114 (P = 0.0132)
MVP		0.23
MPC		0.21
ClinPred		0.30	T
GERP RS		3.4
gMVP		0.16
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs756428356; hg19: chr9-131151692;