1-229508237-C-A

Variant names:

• chr1-229508237-C-A
• rs772323395
• NM_018230.3:c.13G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018230.3(NUP133):​c.13G>T​(p.Ala5Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000725 in 1,379,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. A5T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: NUP133 NM_018230.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06625563).

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.13G>T	p.Ala5Ser	missense	Exon 1 of 26	NP_060700.2
	NUP133-DT	NR_110630.1		n.-193C>A		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP133	ENST00000261396.6	TSL:1 MANE Select	c.13G>T	p.Ala5Ser	missense	Exon 1 of 26	ENSP00000261396.3	Q8WUM0
	NUP133	ENST00000916039.1		c.13G>T	p.Ala5Ser	missense	Exon 1 of 27	ENSP00000586098.1
	NUP133	ENST00000942131.1		c.13G>T	p.Ala5Ser	missense	Exon 1 of 26	ENSP00000612190.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.25e-7 AC: 1 AN: 1379060 Hom.: 0 Cov.: 31 AF XY: 0.00000147 AC XY: 1 AN XY: 681164

African (AFR) AF: 0.00 AC: 0 AN: 29686

American (AMR) AF: 0.00 AC: 0 AN: 29430

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23488

East Asian (EAS) AF: 0.00 AC: 0 AN: 34908

South Asian (SAS) AF: 0.00 AC: 0 AN: 77678

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48504

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5452

European-Non Finnish (NFE) AF: 9.32e-7 AC: 1 AN: 1073090

Other (OTH) AF: 0.00 AC: 0 AN: 56824

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	16
DANN	Benign	0.86
DEOGEN2	Benign	0.080	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		1.5
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.037
Sift	Benign	0.11	T
Sift4G	Benign	0.81	T
Polyphen		0.043	B
Vest4		0.13
MutPred		0.11		Gain of glycosylation at A5 (P = 0.0048)
MVP		0.18
MPC		0.15
ClinPred		0.19	T
GERP RS		4.6
PromoterAI		0.031	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Varity_R		0.12
gMVP		0.23
Mutation Taster		=98/2	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: rs772323395; hg19: chr1-229643984;