2-10600912-G-A

Position:

• chr2-10600912-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024894.4(NOL10):​c.1363C>T​(p.Leu455Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000214 in 1,403,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: NOL10 NM_024894.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.49

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]

NOL10 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35140675).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOL10	NM_024894.4	c.1363C>T	p.Leu455Phe	missense_variant	17/21	ENST00000381685.10	NP_079170.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOL10	ENST00000381685.10	c.1363C>T	p.Leu455Phe	missense_variant	17/21	1	NM_024894.4	ENSP00000371101.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000214 AC: 3 AN: 1403960 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 692924

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000276

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000185

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 10, 2024

The c.1363C>T (p.L455F) alteration is located in exon 17 (coding exon 17) of the NOL10 gene. This alteration results from a C to T substitution at nucleotide position 1363, causing the leucine (L) at amino acid position 455 to be replaced by a phenylalanine (F). 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	0.20
BayesDel_addAF	Uncertain	0.070	D
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.018	.;.;T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.35	T;T;T
MetaSVM	Benign	-0.60	T
MutationAssessor	Uncertain	2.9	.;.;M
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-2.3	N;N;N
REVEL	Benign	0.14
Sift	Benign	0.038	D;D;D
Sift4G	Uncertain	0.049	D;D;D
Polyphen		0.99	D;.;D
Vest4		0.35
MutPred		0.33		.;.;Gain of methylation at K456 (P = 0.0335);
MVP		0.34
MPC		0.49
ClinPred		0.94	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.41
gMVP		0.10

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: rs1463787223; hg19: chr2-10741038;