11-47783075-C-T

Variant summary

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

The NM_015231.3(NUP160):c.4012G>A(p.Glu1338Lys) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: NUP160 NM_015231.3 missense, splice_region
• Scores: Splicing: ADA: 0.8870
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.56

Genes affected

NUP160 (HGNC:18017): (nucleoporin 160) A structural constituent of nuclear pore. Involved in mRNA export from nucleus and nephron development. Part of nuclear pore outer ring. Colocalizes with kinetochore. Implicated in nephrotic syndrome type 19. [provided by Alliance of Genome Resources, Apr 2022]

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=0.40216777).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUP160	NM_015231.3	c.4012G>A	p.Glu1338Lys	missense_variant, splice_region_variant	34/36	ENST00000378460.7
NUP160	NR_134636.3	n.4059G>A		splice_region_variant, non_coding_transcript_exon_variant	34/36

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP160	ENST00000378460.7	c.4012G>A	p.Glu1338Lys	missense_variant, splice_region_variant	34/36	1	NM_015231.3	P1
NUP160	ENST00000694866.1	c.4114G>A	p.Glu1372Lys	missense_variant, splice_region_variant	34/36
NUP160	ENST00000530326.5	c.3883+1847G>A		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Oct 17, 2022

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). This variant has not been reported in the literature in individuals affected with NUP160-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1372 of the NUP160 protein (p.Glu1372Lys). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Benign	-0.36
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.12
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.12
Sift	Benign	0.38	T
Sift4G	Benign	0.42	T
Polyphen		0.038	B
Vest4		0.73
MutPred		0.51		Gain of methylation at E1372 (P = 0.0055);
MVP		0.28
MPC		0.25
ClinPred		0.64	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.89
dbscSNV1_RF	Benign	0.67
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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-47804627;