3-13319092-C-A

Variant names:

• chr3-13319092-C-A
• rs779636166
• NM_024923.4:c.5543G>T

Variant summary

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

The NM_024923.4(NUP210):​c.5543G>T​(p.Ser1848Ile) 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. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S1848R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NUP210 NM_024923.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.24
• 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=0.29519537).

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.5543G>T	p.Ser1848Ile	missense	Exon 39 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.5543G>T	p.Ser1848Ile	missense	Exon 39 of 40	ENSP00000254508.5	Q8TEM1-1
	NUP210	ENST00000916956.1		c.5570G>T	p.Ser1857Ile	missense	Exon 39 of 40	ENSP00000587015.1
	NUP210	ENST00000916951.1		c.5531G>T	p.Ser1844Ile	missense	Exon 39 of 40	ENSP00000587010.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.052	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		2.2
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.057
Sift	Benign	0.032	D
Sift4G	Uncertain	0.040	D
Polyphen		0.97	D
Vest4		0.38
MutPred		0.24		Loss of glycosylation at P1845 (P = 0.0213)
MVP		0.56
MPC		0.30
ClinPred		0.80	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.71
Mutation Taster		=70/30	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: rs779636166; hg19: chr3-13360592;