rs563159052

Variant names:

• chr20-32453754-G-A
• rs563159052
• NM_001256798.2:c.1127C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-32453754-G-A
• chr20-32453754-G-C
• chr20-32453754-G-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001256798.2(NOL4L):​c.1127C>T​(p.Pro376Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000187 in 1,552,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. 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. P376A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: NOL4L NM_001256798.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.21
• Publications: 2 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.17517844).
• BS2: High AC in GnomAdExome4 at 26 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOL4L	NM_001256798.2	c.1127C>T	p.Pro376Leu	missense_variant	Exon 7 of 11	ENST00000621426.7	NP_001243727.1
NOL4L	NM_080616.6	c.395C>T	p.Pro132Leu	missense_variant	Exon 4 of 8		NP_542183.2
NOL4L	NM_001351680.2	c.395C>T	p.Pro132Leu	missense_variant	Exon 4 of 9		NP_001338609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOL4L	ENST00000621426.7	c.1127C>T	p.Pro376Leu	missense_variant	Exon 7 of 11	5	NM_001256798.2	ENSP00000483523.1
NOL4L	ENST00000359676.9	c.395C>T	p.Pro132Leu	missense_variant	Exon 4 of 8	2		ENSP00000352704.5
NOL4L	ENST00000475781.1	n.465C>T		non_coding_transcript_exon_variant	Exon 5 of 7	5		ENSP00000492149.1
ENSG00000236772	ENST00000442179.1	n.*147G>A		downstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152128 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000193 AC: 3 AN: 155084 AF XY: 0.0000244

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000403

Gnomad ASJ exome AF: 0.000117

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000170

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000186 AC: 26 AN: 1400684 Hom.: 0 Cov.: 32 AF XY: 0.0000203 AC XY: 14 AN XY: 690960

African (AFR) AF: 0.00 AC: 0 AN: 31778

American (AMR) AF: 0.0000280 AC: 1 AN: 35748

Ashkenazi Jewish (ASJ) AF: 0.0000794 AC: 2 AN: 25190

East Asian (EAS) AF: 0.00 AC: 0 AN: 35964

South Asian (SAS) AF: 0.00 AC: 0 AN: 79348

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.0000195 AC: 21 AN: 1079528

Other (OTH) AF: 0.0000344 AC: 2 AN: 58070

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152128 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74292

African (AFR) AF: 0.0000241 AC: 1 AN: 41408

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000203 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.077	T;T;.
Eigen	Benign	-0.11
Eigen_PC	Benign	0.019
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-0.80	T
PhyloP100		4.2
PROVEAN	Benign	-2.0	N;.;.
REVEL	Benign	0.098
Sift	Benign	0.045	D;.;.
Sift4G	Uncertain	0.052	T;T;D
Polyphen		0.023	B;.;.
Vest4		0.30
MutPred		0.16		Loss of catalytic residue at P131 (P = 0.0168);.;Loss of catalytic residue at P131 (P = 0.0168);
MVP		0.043
MPC		0.41
ClinPred		0.15	T
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.068
gMVP		0.18
Mutation Taster		=68/32	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

dbSNP: rs563159052; hg19: chr20-31041557;