NM_003787.5:c.514A>G

Variant names:

• chr18-34105061-T-C
• NM_003787.5:c.514A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003787.5(NOL4):​c.514A>G​(p.Thr172Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,452,458 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NOL4 NM_003787.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.94
• Publications: 0 publications found

Genes affected

NOL4 (HGNC:7870): (nucleolar protein 4) Predicted to enable RNA binding activity. Predicted to be located in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03439033).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003787.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOL4	NM_003787.5	MANE Select	c.514A>G	p.Thr172Ala	missense	Exon 3 of 11	NP_003778.2	O94818-1
	NOL4	NM_001384467.1		c.583A>G	p.Thr195Ala	missense	Exon 4 of 12	NP_001371396.1
	NOL4	NM_001384468.1		c.583A>G	p.Thr195Ala	missense	Exon 4 of 11	NP_001371397.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOL4	ENST00000261592.10	TSL:1 MANE Select	c.514A>G	p.Thr172Ala	missense	Exon 3 of 11	ENSP00000261592.4	O94818-1
	NOL4	ENST00000589544.5	TSL:1	c.514A>G	p.Thr172Ala	missense	Exon 3 of 9	ENSP00000465450.1	O94818-2
	NOL4	ENST00000538587.5	TSL:2	c.292A>G	p.Thr98Ala	missense	Exon 3 of 11	ENSP00000443472.1	O94818-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1452458 Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1 AN XY: 723110

African (AFR) AF: 0.00 AC: 0 AN: 33240

American (AMR) AF: 0.0000224 AC: 1 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25988

East Asian (EAS) AF: 0.00 AC: 0 AN: 39568

South Asian (SAS) AF: 0.00 AC: 0 AN: 86064

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 9.06e-7 AC: 1 AN: 1103810

Other (OTH) AF: 0.00 AC: 0 AN: 60032

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	12
DANN	Benign	0.67
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		1.9
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.066
Sift	Benign	1.0	T
Sift4G	Benign	0.90	T
Polyphen		0.0	B
Vest4		0.15
MutPred		0.14		Loss of phosphorylation at T172 (P = 0.0239)
MVP		0.043
MPC		0.076
ClinPred		0.090	T
GERP RS		2.9
Varity_R		0.046
gMVP		0.57
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

hg19: chr18-31685025;