chr3-13321707-C-G

Variant names:

• chr3-13321707-C-G
• rs201360914
• NM_024923.4:c.5044G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024923.4(NUP210):​c.5044G>C​(p.Gly1682Arg) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NUP210 NM_024923.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.420
• Publications: 1 publications found

Genes affected

NUP210 (HGNC:30052): (nucleoporin 210) The nuclear pore complex is a massive structure that extends across the nuclear envelope, forming a gateway that regulates the flow of macromolecules between the nucleus and the cytoplasm. Nucleoporins are the main components of the nuclear pore complex in eukaryotic cells. The protein encoded by this gene is a membrane-spanning glycoprotein that is a major component of the nuclear pore complex. Multiple pseudogenes related to this gene are located on chromosome 3. [provided by RefSeq, Jul 2013]

NUP210 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37267515).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024923.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP210	NM_024923.4	MANE Select	c.5044G>C	p.Gly1682Arg	missense	Exon 36 of 40	NP_079199.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP210	ENST00000254508.7	TSL:2 MANE Select	c.5044G>C	p.Gly1682Arg	missense	Exon 36 of 40	ENSP00000254508.5	Q8TEM1-1
	NUP210	ENST00000916956.1		c.5071G>C	p.Gly1691Arg	missense	Exon 36 of 40	ENSP00000587015.1
	NUP210	ENST00000916951.1		c.5032G>C	p.Gly1678Arg	missense	Exon 36 of 40	ENSP00000587010.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	18
DANN	Benign	0.75
DEOGEN2	Benign	0.049	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.37	N
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.42
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.10
Sift	Benign	0.93	T
Sift4G	Benign	0.49	T
Polyphen		0.99	D
Vest4		0.47
MutPred		0.55		Loss of catalytic residue at A1683 (P = 0.0914)
MVP		0.37
MPC		0.43
ClinPred		0.41	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.084
gMVP		0.51
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs201360914; hg19: chr3-13363207;