22-37691295-C-G

Variant names:

• chr22-37691295-C-G
• rs757854451
• NM_024313.3:c.601C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024313.3(NOL12):​c.601C>G​(p.Arg201Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R201C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NOL12 NM_024313.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.67
• Publications: 4 publications found

Genes affected

NOL12 (HGNC:28585): (nucleolar protein 12) Enables identical protein binding activity. Predicted to be active in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000100101 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024313.3. 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
	NOL12	NM_024313.3	MANE Select	c.601C>G	p.Arg201Gly	missense	Exon 6 of 6	NP_077289.1	Q9UGY1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOL12	ENST00000359114.9	TSL:1 MANE Select	c.601C>G	p.Arg201Gly	missense	Exon 6 of 6	ENSP00000352021.4	Q9UGY1
	NOL12	ENST00000611699.1	TSL:1	c.601C>G	p.Arg201Gly	missense	Exon 6 of 7	ENSP00000482349.1	Q9UGY1
	NOL12	ENST00000438329.5	TSL:1	n.601C>G		non_coding_transcript_exon	Exon 6 of 7	ENSP00000403059.1	Q9UGY1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.54	D
Eigen	Benign	0.15
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Uncertain	0.10	D
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.7
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.4	D
REVEL	Pathogenic	0.66
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.84	P
Vest4		0.53
MutPred		0.49		Gain of methylation at R202 (P = 0.0367)
MVP		0.90
MPC		0.81
ClinPred		0.97	D
GERP RS		5.1
Varity_R		0.75
gMVP		0.25
Mutation Taster		=32/68	disease causing

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

dbSNP: rs757854451; hg19: chr22-38087302;