17-75208582-G-C

Position:

• chr17-75208582-G-C

Variant summary

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

The NM_024844.5(NUP85):​c.89G>C​(p.Gly30Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,457,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: NUP85 NM_024844.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.08

Genes affected

NUP85 (HGNC:8734): (nucleoporin 85) This gene encodes a protein component of the Nup107-160 subunit of the nuclear pore complex. Nuclear pore complexes are embedded in the nuclear envelope and promote bidirectional transport of macromolecules between the cytoplasm and nucleus. The encoded protein can also bind to the C-terminus of chemokine (C-C motif) receptor 2 (CCR2) and promote chemotaxis of monocytes, thereby participating in the inflammatory response. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

NUP85 (HGNC:):

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=0.275183).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUP85	NM_024844.5	c.89G>C	p.Gly30Ala	missense_variant	2/19	ENST00000245544.9	NP_079120.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUP85	ENST00000245544.9	c.89G>C	p.Gly30Ala	missense_variant	2/19	1	NM_024844.5	ENSP00000245544.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457476 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 725254

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 02, 2024

This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 30 of the NUP85 protein (p.Gly30Ala). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NUP85-related conditions. ClinVar contains an entry for this variant (Variation ID: 2112463). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	23
DANN	Benign	0.89
DEOGEN2	Benign	0.063	T;T;T
Eigen	Benign	-0.042
Eigen_PC	Benign	0.023
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.78	T;T;T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.28	T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.7	.;L;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-2.1	.;N;.
REVEL	Benign	0.12
Sift	Benign	0.081	.;T;.
Sift4G	Benign	0.20	T;T;T
Polyphen		0.41	.;B;.
Vest4		0.27, 0.28
MutPred		0.68		.;Gain of stability (P = 0.1045);Gain of stability (P = 0.1045);
MVP		0.10
MPC		0.44
ClinPred		0.53	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: chr17-73204677;