chr3-13319940-C-T

Position:

• chr3-13319940-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024923.4(NUP210):​c.5206G>A​(p.Glu1736Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 5.38

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=0.38220397).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUP210	NM_024923.4	c.5206G>A	p.Glu1736Lys	missense_variant	37/40	ENST00000254508.7	NP_079199.2
NUP210	XM_047447795.1	c.2590G>A	p.Glu864Lys	missense_variant	19/22		XP_047303751.1
NUP210	XM_047447797.1	c.2557G>A	p.Glu853Lys	missense_variant	19/22		XP_047303753.1
NUP210	XM_047447796.1	c.2521G>A	p.Glu841Lys	missense_variant	19/22		XP_047303752.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUP210	ENST00000254508.7	c.5206G>A	p.Glu1736Lys	missense_variant	37/40	2	NM_024923.4	ENSP00000254508	P1
NUP210	ENST00000695489.1	n.934G>A		non_coding_transcript_exon_variant	1/4
NUP210	ENST00000695490.1	c.*634G>A		3_prime_UTR_variant, NMD_transcript_variant	19/22			ENSP00000511960

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

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

Aug 16, 2022

The c.5206G>A (p.E1736K) alteration is located in exon 37 (coding exon 37) of the NUP210 gene. This alteration results from a G to A substitution at nucleotide position 5206, causing the glutamic acid (E) at amino acid position 1736 to be replaced by a lysine (K). 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	0.18
BayesDel_addAF	Benign	0.00065	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.047	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.17
Sift	Benign	0.41	T
Sift4G	Benign	0.30	T
Polyphen		0.95	P
Vest4		0.49
MutPred		0.38		Loss of ubiquitination at K1735 (P = 0.0157);
MVP		0.46
MPC		0.28
ClinPred		0.68	D
GERP RS		5.5
Varity_R		0.33
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1044373551; hg19: chr3-13361440;