chr2-202297473-C-T

Variant names:

• chr2-202297473-C-T
• NM_015934.5:c.1166C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015934.5(NOP58):​c.1166C>T​(p.Ala389Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NOP58 NM_015934.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.83
• Publications: 0 publications found

Genes affected

NOP58 (HGNC:29926): (NOP58 ribonucleoprotein) The protein encoded by this gene is a core component of box C/D small nucleolar ribonucleoproteins. Some box C/D small nucleolar RNAs (snoRNAs), such as U3, U8, and U14, are dependent upon the encoded protein for their synthesis. This protein is SUMOylated, which is necessary for high affinity binding to snoRNAs. [provided by RefSeq, Nov 2015]

ENSG00000286223 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30980006).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015934.5. 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
	NOP58	NM_015934.5	MANE Select	c.1166C>T	p.Ala389Val	missense	Exon 11 of 15	NP_057018.1	Q9Y2X3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOP58	ENST00000264279.10	TSL:1 MANE Select	c.1166C>T	p.Ala389Val	missense	Exon 11 of 15	ENSP00000264279.5	Q9Y2X3
	NOP58	ENST00000919441.1		c.1166C>T	p.Ala389Val	missense	Exon 11 of 16	ENSP00000589500.1
	NOP58	ENST00000919443.1		c.1151C>T	p.Ala384Val	missense	Exon 11 of 15	ENSP00000589502.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Benign	0.044
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	1.8	L
PhyloP100		5.8
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-2.5	N
REVEL	Uncertain	0.32
Sift	Benign	0.30	T
Sift4G	Benign	0.22	T
Polyphen		0.011	B
Vest4		0.44
MutPred		0.46		Loss of ubiquitination at K390 (P = 0.058)
MVP		0.61
MPC		0.49
ClinPred		0.93	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.086
gMVP		0.38
Mutation Taster		=69/31	polymorphism

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

Other links and lift over

hg19: chr2-203162196;