rs779636166

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr3-13319092-C-T
• chr3-13319092-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024923.4(NUP210):​c.5543G>A​(p.Ser1848Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,454,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). 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)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: NUP210 NM_024923.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18207783).

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>A	p.Ser1848Asn	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>A	p.Ser1848Asn	missense	Exon 39 of 40	ENSP00000254508.5	Q8TEM1-1
	NUP210	ENST00000916956.1		c.5570G>A	p.Ser1857Asn	missense	Exon 39 of 40	ENSP00000587015.1
	NUP210	ENST00000916951.1		c.5531G>A	p.Ser1844Asn	missense	Exon 39 of 40	ENSP00000587010.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000255 AC: 6 AN: 235542 AF XY: 0.0000158

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000342

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1454252 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 722422

African (AFR) AF: 0.00 AC: 0 AN: 33416

American (AMR) AF: 0.00 AC: 0 AN: 43346

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25724

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39482

South Asian (SAS) AF: 0.00 AC: 0 AN: 84124

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52990

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109376

Other (OTH) AF: 0.00 AC: 0 AN: 60076

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

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	0.10
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.035	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		2.2
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.080
Sift	Benign	0.077	T
Sift4G	Benign	0.16	T
Polyphen		0.97	D
Vest4		0.28
MutPred		0.23		Loss of glycosylation at P1845 (P = 0.0213)
MVP		0.48
MPC		0.21
ClinPred		0.17	T
GERP RS		5.5
Varity_R		0.078
gMVP		0.53
Mutation Taster		=83/17	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;