2-10589129-T-C

Position:

• chr2-10589129-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_024894.4(NOL10):​c.1758A>G​(p.Thr586=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00177 in 1,614,040 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0010 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (3 hom.)
• Consequence: NOL10 NM_024894.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.25

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-10589129-T-C is Benign according to our data. Variant chr2-10589129-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2650678.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.25 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOL10	NM_024894.4	c.1758A>G	p.Thr586=	synonymous_variant	19/21	ENST00000381685.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOL10	ENST00000381685.10	c.1758A>G	p.Thr586=	synonymous_variant	19/21	1	NM_024894.4	P1
	ENST00000414538.1			upstream_gene_variant		4

Frequencies

GnomAD3 genomes AF: 0.00104 AC: 159 AN: 152218 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00173

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.000908 AC: 228 AN: 251126 Hom.: 0 AF XY: 0.000906 AC XY: 123 AN XY: 135716

Gnomad AFR exome AF: 0.000492

Gnomad AMR exome AF: 0.000347

Gnomad ASJ exome AF: 0.00348

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.00140

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00184 AC: 2690 AN: 1461704 Hom.: 3 Cov.: 31 AF XY: 0.00174 AC XY: 1264 AN XY: 727132

Gnomad4 AFR exome AF: 0.000149

Gnomad4 AMR exome AF: 0.000470

Gnomad4 ASJ exome AF: 0.00344

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.000243

Gnomad4 NFE exome AF: 0.00218

Gnomad4 OTH exome AF: 0.00215

GnomAD4 genome AF: 0.00104 AC: 159 AN: 152336 Hom.: 0 Cov.: 32 AF XY: 0.000980 AC XY: 73 AN XY: 74508

Gnomad4 AFR AF: 0.000409

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.00375

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00173

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.00157 Hom.: 0

Bravo AF: 0.00109

EpiCase AF: 0.00191

EpiControl AF: 0.00154

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

NOL10: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.041
DANN	Benign	0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

LitVar

Other links and lift over

dbSNP: rs140097585; hg19: chr2-10729255;