chr2-231461706-C-G

Variant names:

• chr2-231461706-C-G
• rs1131171
• NM_005381.3:c.447G>C

Variant summary

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

The NM_005381.3(NCL):​c.447G>C​(p.Glu149Asp) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NCL NM_005381.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.38
• Publications: 28 publications found

Genes affected

NCL (HGNC:7667): (nucleolin) Nucleolin (NCL), a eukaryotic nucleolar phosphoprotein, is involved in the synthesis and maturation of ribosomes. It is located mainly in dense fibrillar regions of the nucleolus. Human NCL gene consists of 14 exons with 13 introns and spans approximately 11kb. The intron 11 of the NCL gene encodes a small nucleolar RNA, termed U20. [provided by RefSeq, Jul 2008]

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=0.034300983).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCL	NM_005381.3	c.447G>C	p.Glu149Asp	missense_variant	Exon 3 of 14	ENST00000322723.9	NP_005372.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCL	ENST00000322723.9	c.447G>C	p.Glu149Asp	missense_variant	Exon 3 of 14	2	NM_005381.3	ENSP00000318195.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.0010
DANN	Benign	0.97
DEOGEN2	Benign	0.17	T;T;T;.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.60	T;T;T;T;T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.034	T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.72	N;.;.;.;.
PhyloP100		-6.4
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.83	N;N;N;N;N
REVEL	Benign	0.088
Sift	Benign	0.24	T;D;D;D;D
Sift4G	Benign	0.55	T;.;T;.;.
Polyphen		0.0	B;.;.;.;.
Vest4		0.10
MutPred		0.034		Loss of helix (P = 0.1299);.;.;.;.;
MVP		0.26
MPC		0.023
ClinPred		0.16	T
GERP RS		-3.4
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		3.9
Varity_R		0.062
gMVP		0.027
Mutation Taster		=87/13	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: rs1131171; hg19: chr2-232326417;