chr9-92314320-G-C

Position:

• chr9-92314320-G-C

Variant summary

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

The NM_017948.6(NOL8):​c.2305C>G​(p.Gln769Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NOL8 NM_017948.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.65

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]

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=0.2644617).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOL8	NM_017948.6	c.2305C>G	p.Gln769Glu	missense_variant	7/17	ENST00000442668.7	NP_060418.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOL8	ENST00000442668.7	c.2305C>G	p.Gln769Glu	missense_variant	7/17	1	NM_017948.6	ENSP00000401177	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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

Jun 24, 2022

The c.2305C>G (p.Q769E) alteration is located in exon 7 (coding exon 6) of the NOL8 gene. This alteration results from a C to G substitution at nucleotide position 2305, causing the glutamine (Q) at amino acid position 769 to be replaced by a glutamic acid (E). 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	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	T;.;T;.;.;T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.89	.;D;D;D;.;D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.26	T;T;T;T;T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.8	L;.;L;L;.;.
MutationTaster	Benign	0.95	D;D;D;D;D
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.8	N;N;N;N;N;N
REVEL	Benign	0.084
Sift	Uncertain	0.0070	D;D;D;D;D;D
Sift4G	Uncertain	0.018	D;D;D;D;D;.
Polyphen		0.80	P;.;P;.;.;.
Vest4		0.22
MutPred		0.27		Loss of MoRF binding (P = 0.0286);.;Loss of MoRF binding (P = 0.0286);Loss of MoRF binding (P = 0.0286);.;Loss of MoRF binding (P = 0.0286);
MVP		0.45
MPC		0.13
ClinPred		0.71	D
GERP RS		4.4
Varity_R		0.14
gMVP		0.091

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: rs1839146358; hg19: chr9-95076602;