20-32447731-C-G

Variant summary

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

The NM_001256798.2(NOL4L):c.1908G>C(p.Arg636Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/18 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)
• Consequence: NOL4L NM_001256798.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.93

Genes affected

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

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=0.16224143).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOL4L	NM_001256798.2	c.1908G>C	p.Arg636Ser	missense_variant	11/11	ENST00000621426.7
NOL4L	NM_080616.6	c.1176G>C	p.Arg392Ser	missense_variant	8/8
NOL4L	NM_001351680.2	c.*65G>C		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOL4L	ENST00000621426.7	c.1908G>C	p.Arg636Ser	missense_variant	11/11	5	NM_001256798.2	P1
NOL4L	ENST00000359676.9	c.1176G>C	p.Arg392Ser	missense_variant	8/8	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

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

Nov 27, 2023

The c.1176G>C (p.R392S) alteration is located in exon 8 (coding exon 7) of the NOL4L gene. This alteration results from a G to C substitution at nucleotide position 1176, causing the arginine (R) at amino acid position 392 to be replaced by a serine (S). 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	0.34
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.30
Cadd	Benign	22
Dann	Uncertain	1.0
DEOGEN2	Benign	0.067	T;T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.75	T
MutationTaster	Benign	0.93	D
PROVEAN	Benign	-1.6	N;.
REVEL	Benign	0.059
Sift	Benign	0.061	T;.
Sift4G	Benign	0.19	T;T
Polyphen		0.40	B;.
Vest4		0.29
MutPred		0.25		Gain of glycosylation at R392 (P = 0.001);.;
MVP		0.043
MPC		0.63
ClinPred		0.89	D
GERP RS		4.9
Varity_R		0.30
gMVP		0.37

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-31035534;