2-202292790-C-G

Variant names:

• chr2-202292790-C-G
• NM_015934.5:c.794C>G

Variant summary

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

The NM_015934.5(NOP58):​c.794C>G​(p.Ser265Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: NOP58 NM_015934.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.60

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]

ACMG classification

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
NOP58	NM_015934.5	c.794C>G	p.Ser265Cys	missense_variant	Exon 9 of 15	ENST00000264279.10	NP_057018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOP58	ENST00000264279.10	c.794C>G	p.Ser265Cys	missense_variant	Exon 9 of 15	1	NM_015934.5	ENSP00000264279.5
NOP58	ENST00000433543.2	n.404C>G		non_coding_transcript_exon_variant	Exon 5 of 7	3		ENSP00000388126.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.794C>G (p.S265C) alteration is located in exon 9 (coding exon 9) of the NOP58 gene. This alteration results from a C to G substitution at nucleotide position 794, causing the serine (S) at amino acid position 265 to be replaced by a cysteine (C). 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	0.21
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	26
DANN	Uncertain	0.98
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.075	D
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.33	T
MutationAssessor	Pathogenic	3.4	M
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.019	D
Polyphen		0.062	B
Vest4		0.66
MutPred		0.65		Loss of disorder (P = 0.4036);
MVP		0.55
MPC		1.1
ClinPred		0.97	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.27
gMVP		0.39

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-203157513;