1-229508148-C-A

Variant names:

• chr1-229508148-C-A
• rs751157872
• NM_018230.3:c.102G>T

Variant summary

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

The NM_018230.3(NUP133):​c.102G>T​(p.Arg34Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NUP133 NM_018230.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.626
• Publications: 0 publications found

Genes affected

NUP133 (HGNC:18016): (nucleoporin 133) The nuclear envelope creates distinct nuclear and cytoplasmic compartments in eukaryotic cells. It consists of two concentric membranes perforated by nuclear pores, large protein complexes that form aqueous channels to regulate the flow of macromolecules between the nucleus and the cytoplasm. These complexes are composed of at least 100 different polypeptide subunits, many of which belong to the nucleoporin family. The nucleoporin protein encoded by this gene displays evolutionarily conserved interactions with other nucleoporins. This protein, which localizes to both sides of the nuclear pore complex at interphase, remains associated with the complex during mitosis and is targeted at early stages to the reforming nuclear envelope. This protein also localizes to kinetochores of mitotic cells. [provided by RefSeq, Jul 2008]

NUP133-DT (HGNC:55870): (NUP133 divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018230.3. 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
	NUP133	NM_018230.3	MANE Select	c.102G>T	p.Arg34Ser	missense	Exon 1 of 26	NP_060700.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP133	ENST00000261396.6	TSL:1 MANE Select	c.102G>T	p.Arg34Ser	missense	Exon 1 of 26	ENSP00000261396.3	Q8WUM0
	NUP133	ENST00000916039.1		c.102G>T	p.Arg34Ser	missense	Exon 1 of 27	ENSP00000586098.1
	NUP133	ENST00000942131.1		c.102G>T	p.Arg34Ser	missense	Exon 1 of 26	ENSP00000612190.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.10
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.73	T
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.63
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.19
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.63
MutPred		0.47		Loss of MoRF binding (P = 0.0093)
MVP		0.48
MPC		0.61
ClinPred		0.99	D
GERP RS		2.4
PromoterAI		-0.088	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.46
gMVP		0.71
Mutation Taster		=60/40	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: rs751157872; hg19: chr1-229643895; COSMIC: COSV104547362; COSMIC: COSV104547362;