rs1373080489

Variant names:

• chr2-10589238-C-T
• rs1373080489
• NM_024894.4:c.1649G>A

Variant summary

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

The NM_024894.4(NOL10):​c.1649G>A​(p.Ser550Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,694 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NOL10 NM_024894.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.68
• Publications: 0 publications found

Genes affected

NOL10 (HGNC:25862): (nucleolar protein 10) Enables RNA binding activity. Predicted to be involved in maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA). Located in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000234818 (HGNC:):

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=0.23102653).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024894.4. 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
	NOL10	NM_024894.4	MANE Select	c.1649G>A	p.Ser550Asn	missense	Exon 19 of 21	NP_079170.2	Q9BSC4-1
	NOL10	NM_001261392.2		c.1571G>A	p.Ser524Asn	missense	Exon 18 of 20	NP_001248321.1	Q9BSC4-4
	NOL10	NM_001261394.2		c.1499G>A	p.Ser500Asn	missense	Exon 18 of 20	NP_001248323.1	Q9BSC4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOL10	ENST00000381685.10	TSL:1 MANE Select	c.1649G>A	p.Ser550Asn	missense	Exon 19 of 21	ENSP00000371101.5	Q9BSC4-1
	NOL10	ENST00000695468.1		c.1700G>A	p.Ser567Asn	missense	Exon 20 of 22	ENSP00000511946.1	A0A8Q3SHX7
	NOL10	ENST00000928635.1		c.1670G>A	p.Ser557Asn	missense	Exon 19 of 21	ENSP00000598694.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461694 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727130

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111866

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

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	0.20
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.010	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.8	L
PhyloP100		3.7
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.060
Sift	Benign	0.030	D
Sift4G	Uncertain	0.022	D
Polyphen		0.45	B
Vest4		0.42
MutPred		0.15		Loss of phosphorylation at S550 (P = 0.001)
MVP		0.55
MPC		0.38
ClinPred		0.85	D
GERP RS		4.8
Varity_R		0.25
gMVP		0.14
Mutation Taster		=85/15	polymorphism

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

Other links and lift over

dbSNP: rs1373080489; hg19: chr2-10729364;