9-92298930-C-G

Position:

• chr9-92298930-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017948.6(NOL8):​c.3327G>C​(p.Glu1109Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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: 32)
• Consequence: NOL8 NM_017948.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.557

Genes affected

NOL8 (HGNC:23387): (nucleolar protein 8) NOL8 binds Ras-related GTP-binding proteins (see MIM 608267) and plays a role in cell growth (Sekiguchi et al., 2004 [PubMed 14660641]).[supplied by OMIM, Mar 2008]

NOL8 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056073636).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOL8	NM_017948.6	c.3327G>C	p.Glu1109Asp	missense_variant	15/17	ENST00000442668.7	NP_060418.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOL8	ENST00000442668.7	c.3327G>C	p.Glu1109Asp	missense_variant	15/17	1	NM_017948.6	ENSP00000401177.2
NOL8	ENST00000542053.5	c.3123G>C	p.Glu1041Asp	missense_variant	14/16	5		ENSP00000440709.1
NOL8	ENST00000360868.7	n.*3182G>C		non_coding_transcript_exon_variant	15/17	2		ENSP00000354115.3
NOL8	ENST00000360868.7	n.*3182G>C		3_prime_UTR_variant	15/17	2		ENSP00000354115.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

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

Aug 12, 2024

The c.3327G>C (p.E1109D) alteration is located in exon 15 (coding exon 14) of the NOL8 gene. This alteration results from a G to C substitution at nucleotide position 3327, causing the glutamic acid (E) at amino acid position 1109 to be replaced by an aspartic acid (D). 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	0.13
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0034	T;.;T;.;.
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.77	.;T;T;T;.
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.056	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M;.;M;.;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.0	N;N;N;N;N
REVEL	Benign	0.015
Sift	Uncertain	0.023	D;D;D;T;D
Sift4G	Benign	0.21	T;T;T;T;T
Polyphen		0.36	B;B;B;.;B
Vest4		0.10
MutPred		0.14		Loss of methylation at K1108 (P = 0.1098);.;Loss of methylation at K1108 (P = 0.1098);.;.;
MVP		0.29
MPC		0.074
ClinPred		0.055	T
GERP RS		1.4
Varity_R		0.080
gMVP		0.026

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr9-95061212;