rs776088625

Variant names:

• chr20-32452304-C-A
• rs776088625
• NM_001256798.2:c.1754G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-32452304-C-A
• chr20-32452304-C-T

Variant summary

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

The NM_001256798.2(NOL4L):​c.1754G>T​(p.Arg585Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,762 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R585H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: NOL4L NM_001256798.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.34
• Publications: 0 publications found

Genes affected

NOL4L (HGNC:16106): (nucleolar protein 4 like) Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000236772 (HGNC:):

ACMG classification

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

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOL4L	NM_001256798.2	c.1754G>T	p.Arg585Leu	missense_variant	Exon 10 of 11	ENST00000621426.7	NP_001243727.1
NOL4L	NM_080616.6	c.1022G>T	p.Arg341Leu	missense_variant	Exon 7 of 8		NP_542183.2
NOL4L	NM_001351680.2	c.1022G>T	p.Arg341Leu	missense_variant	Exon 7 of 9		NP_001338609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOL4L	ENST00000621426.7	c.1754G>T	p.Arg585Leu	missense_variant	Exon 10 of 11	5	NM_001256798.2	ENSP00000483523.1
ENSG00000236772	ENST00000442179.1	n.716+591C>A		intron_variant	Intron 3 of 3	1
NOL4L	ENST00000359676.9	c.1022G>T	p.Arg341Leu	missense_variant	Exon 7 of 8	2		ENSP00000352704.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455762 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 723878

African (AFR) AF: 0.00 AC: 0 AN: 33302

American (AMR) AF: 0.00 AC: 0 AN: 44026

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25768

East Asian (EAS) AF: 0.00 AC: 0 AN: 39450

South Asian (SAS) AF: 0.00 AC: 0 AN: 85308

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53194

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5732

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108834

Other (OTH) AF: 0.00 AC: 0 AN: 60148

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.34
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T;T;.
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.70	D;D;D
MetaSVM	Uncertain	-0.21	T
PhyloP100		7.3
PROVEAN	Benign	-2.1	N;.;.
REVEL	Benign	0.27
Sift	Uncertain	0.015	D;.;.
Sift4G	Benign	0.19	T;T;D
Polyphen		1.0	D;.;.
Vest4		0.90
MutPred		0.44		Gain of sheet (P = 0.0477);.;Gain of sheet (P = 0.0477);
MVP		0.082
MPC		0.40
ClinPred		0.92	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.34
gMVP		0.57
Mutation Taster		=31/69	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs776088625; hg19: chr20-31040107;