9-92310605-T-C

Position:

• chr9-92310605-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017948.6(NOL8):​c.2543A>G​(p.Asp848Gly) 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. 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: 4.15

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26348424).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOL8	NM_017948.6	c.2543A>G	p.Asp848Gly	missense_variant	9/17	ENST00000442668.7	NP_060418.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOL8	ENST00000442668.7	c.2543A>G	p.Asp848Gly	missense_variant	9/17	1	NM_017948.6	ENSP00000401177.2
NOL8	ENST00000542053.5	c.2339A>G	p.Asp780Gly	missense_variant	8/16	5		ENSP00000440709.1
NOL8	ENST00000432670.6	c.2543A>G	p.Asp848Gly	missense_variant	9/13	5		ENSP00000414112.2
NOL8	ENST00000360868.7	n.*2398A>G		non_coding_transcript_exon_variant	9/17	2		ENSP00000354115.3
NOL8	ENST00000434228.5	n.*2835A>G		non_coding_transcript_exon_variant	11/13	2		ENSP00000415750.1
NOL8	ENST00000360868.7	n.*2398A>G		3_prime_UTR_variant	9/17	2		ENSP00000354115.3
NOL8	ENST00000434228.5	n.*2835A>G		3_prime_UTR_variant	11/13	2		ENSP00000415750.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Oct 16, 2024

The c.2543A>G (p.D848G) alteration is located in exon 9 (coding exon 8) of the NOL8 gene. This alteration results from a A to G substitution at nucleotide position 2543, causing the aspartic acid (D) at amino acid position 848 to be replaced by a glycine (G). 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	0.19
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.055	T;.;T;.;.;T
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	.;D;D;D;.;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.26	T;T;T;T;T;T
MetaSVM	Benign	-0.49	T
MutationAssessor	Pathogenic	3.0	M;.;M;.;.;.
PrimateAI	Benign	0.34	T
PROVEAN	Pathogenic	-5.0	D;D;D;D;D;D
REVEL	Benign	0.25
Sift	Uncertain	0.0060	D;D;D;D;D;D
Sift4G	Uncertain	0.0070	D;D;D;D;D;.
Polyphen		1.0	D;D;D;.;D;.
Vest4		0.20
MutPred		0.12		Gain of relative solvent accessibility (P = 0.0479);.;Gain of relative solvent accessibility (P = 0.0479);.;.;Gain of relative solvent accessibility (P = 0.0479);
MVP		0.59
MPC		0.29
ClinPred		1.0	D
GERP RS		5.9
Varity_R		0.61
gMVP		0.20

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: rs866639148; hg19: chr9-95072887;