rs749214861

Variant names:

• chr2-10589586-G-A
• rs749214861
• NM_024894.4:c.1588C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-10589586-G-A
• chr2-10589586-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_024894.4(NOL10):​c.1588C>T​(p.Arg530Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000016 in 1,560,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: NOL10 NM_024894.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.60
• Publications: 5 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10693681).

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.1588C>T	p.Arg530Cys	missense	Exon 18 of 21	NP_079170.2	Q9BSC4-1
	NOL10	NM_001261392.2		c.1510C>T	p.Arg504Cys	missense	Exon 17 of 20	NP_001248321.1	Q9BSC4-4
	NOL10	NM_001261394.2		c.1438C>T	p.Arg480Cys	missense	Exon 17 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.1588C>T	p.Arg530Cys	missense	Exon 18 of 21	ENSP00000371101.5	Q9BSC4-1
	NOL10	ENST00000695468.1		c.1639C>T	p.Arg547Cys	missense	Exon 19 of 22	ENSP00000511946.1	A0A8Q3SHX7
	NOL10	ENST00000928635.1		c.1609C>T	p.Arg537Cys	missense	Exon 18 of 21	ENSP00000598694.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152064 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

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

GnomAD2 exomes AF: 0.0000242 AC: 5 AN: 206324 AF XY: 0.0000268

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: 0.0000403

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000163 AC: 23 AN: 1408648 Hom.: 0 Cov.: 30 AF XY: 0.0000229 AC XY: 16 AN XY: 697942

African (AFR) AF: 0.0000326 AC: 1 AN: 30688

American (AMR) AF: 0.00 AC: 0 AN: 31688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23652

East Asian (EAS) AF: 0.00 AC: 0 AN: 39058

South Asian (SAS) AF: 0.000185 AC: 14 AN: 75504

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51820

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5496

European-Non Finnish (NFE) AF: 0.00000549 AC: 6 AN: 1092646

Other (OTH) AF: 0.0000344 AC: 2 AN: 58096

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152064 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74280

African (AFR) AF: 0.0000242 AC: 1 AN: 41396

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000452 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000247 AC: 3

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	0.086
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.0032	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.31
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.69	N
PhyloP100		2.6
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.075
Sift	Benign	0.053	T
Sift4G	Uncertain	0.050	T
Polyphen		0.38	B
Vest4		0.19
MutPred		0.17		Loss of solvent accessibility (P = 0.0404)
MVP		0.30
MPC		0.16
ClinPred		0.16	T
GERP RS		4.8
Varity_R		0.070
gMVP		0.039
Mutation Taster		=89/11	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: rs749214861; hg19: chr2-10729712; COSMIC: COSV62038825;