chr3-13321707-C-G

Position:

• chr3-13321707-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 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. 15/21 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUP210	NM_024923.4	c.5044G>C	p.Gly1682Arg	missense_variant	36/40	ENST00000254508.7
NUP210	XM_047447795.1	c.2428G>C	p.Gly810Arg	missense_variant	18/22
NUP210	XM_047447797.1	c.2395G>C	p.Gly799Arg	missense_variant	18/22
NUP210	XM_047447796.1	c.2359G>C	p.Gly787Arg	missense_variant	18/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP210	ENST00000254508.7	c.5044G>C	p.Gly1682Arg	missense_variant	36/40	2	NM_024923.4	P1
NUP210	ENST00000695491.1	n.3046G>C		non_coding_transcript_exon_variant	22/22
NUP210	ENST00000695490.1	c.*472G>C		3_prime_UTR_variant, NMD_transcript_variant	18/22

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Apr 29, 2024

The c.5044G>C (p.G1682R) alteration is located in exon 36 (coding exon 36) of the NUP210 gene. This alteration results from a G to C substitution at nucleotide position 5044, causing the glycine (G) at amino acid position 1682 to be replaced by an arginine (R). 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	0.14
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
MutationTaster	Benign	1.0	N
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs201360914; hg19: chr3-13363207;