20-32447727-C-G

Variant names:

• chr20-32447727-C-G
• rs761373270
• NM_001256798.2:c.1912G>C

Variant summary

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

The NM_001256798.2(NOL4L):​c.1912G>C​(p.Val638Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000331 in 1,207,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 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. V638M) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000033 (0 hom.)
• Consequence: NOL4L NM_001256798.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16
• 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]

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=0.039396405).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOL4L	NM_001256798.2	c.1912G>C	p.Val638Leu	missense_variant	Exon 11 of 11	ENST00000621426.7	NP_001243727.1
NOL4L	NM_080616.6	c.1180G>C	p.Val394Leu	missense_variant	Exon 8 of 8		NP_542183.2
NOL4L	NM_001351680.2	c.*69G>C		3_prime_UTR_variant	Exon 9 of 9		NP_001338609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOL4L	ENST00000621426.7	c.1912G>C	p.Val638Leu	missense_variant	Exon 11 of 11	5	NM_001256798.2	ENSP00000483523.1
NOL4L	ENST00000359676.9	c.1180G>C	p.Val394Leu	missense_variant	Exon 8 of 8	2		ENSP00000352704.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000331 AC: 4 AN: 1207070 Hom.: 0 Cov.: 33 AF XY: 0.00000335 AC XY: 2 AN XY: 597490

African (AFR) AF: 0.00 AC: 0 AN: 26308

American (AMR) AF: 0.00 AC: 0 AN: 37028

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17462

East Asian (EAS) AF: 0.00 AC: 0 AN: 20326

South Asian (SAS) AF: 0.00 AC: 0 AN: 82370

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34004

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3328

European-Non Finnish (NFE) AF: 0.00000425 AC: 4 AN: 942030

Other (OTH) AF: 0.00 AC: 0 AN: 44214

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	16
DANN	Benign	0.86
DEOGEN2	Benign	0.024	T;T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.69
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.85	T;T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.039	T;T
MetaSVM	Benign	-1.0	T
PhyloP100		1.2
PROVEAN	Benign	0.70	N;.
REVEL	Benign	0.023
Sift	Benign	0.98	T;.
Sift4G	Benign	1.0	T;T
Polyphen		0.0010	B;.
Vest4		0.13
MutPred		0.13		Gain of catalytic residue at V394 (P = 0.0642);.;
MVP		0.043
MPC		0.23
ClinPred		0.079	T
GERP RS		2.6
Varity_R		0.027
gMVP		0.20
Mutation Taster		=95/5	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: rs761373270; hg19: chr20-31035530; COSMIC: COSV105265547; COSMIC: COSV105265547;