12-68689593-G-A

Position:

chr12-68689593-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020401.4(NUP107):c.161G>A(p.Arg54Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000776 in 1,611,460 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00080 ( 0 hom. )

Consequence

NUP107
NM_020401.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 2.92

Variant links:

Genes affected

NUP107 (HGNC:29914): (nucleoporin 107) This gene encodes a member of the nucleoporin family. The protein is localized to the nuclear rim and is an essential component of the nuclear pore complex (NPC). All molecules entering or leaving the nucleus either diffuse through or are actively transported by the NPC. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [provided by RefSeq, Jul 2008]

NUP107 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUP107	NM_020401.4 link	c.161G>A	p.Arg54Gln	missense_variant	3/28	ENST00000229179.9	NP_065134.1	P57740-1
NUP107	NM_001330192.2 link	c.46G>A	p.Glu16Lys	missense_variant	3/28		NP_001317121.1	P57740-2
NUP107	XM_005269037.5 link	c.161G>A	p.Arg54Gln	missense_variant	3/27		XP_005269094.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUP107	ENST00000229179.9 link	c.161G>A	p.Arg54Gln	missense_variant	3/28	1	NM_020401.4	ENSP00000229179.4		P57740-1

Frequencies

GnomAD3 genomes

AF:

0.000513

AC:

AN:

151990

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000190

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000971

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000493

AC:

123

AN:

249514

Hom.:

AF XY:

0.000430

AC XY:

AN XY:

134954

show subpopulations

Gnomad AFR exome

AF:

0.000186

Gnomad AMR exome

AF:

0.000559

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000330

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000840

Gnomad OTH exome

AF:

0.000659

GnomAD4 exome

AF:

0.000803

AC:

1172

AN:

1459352

Hom.:

Cov.:

AF XY:

0.000773

AC XY:

561

AN XY:

726038

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.000564

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.000996

Gnomad4 OTH exome

AF:

0.000498

GnomAD4 genome

AF:

0.000513

AC:

AN:

152108

Hom.:

Cov.:

AF XY:

0.000444

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000190

Gnomad4 NFE

AF:

0.000971

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000854

Hom.:

Bravo

AF:

0.000570

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.000535

AC:

EpiCase

AF:

0.000988

EpiControl

AF:

0.000952

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 17, 2021

The c.161G>A (p.R54Q) alteration is located in exon 3 (coding exon 3) of the NUP107 gene. This alteration results from a G to A substitution at nucleotide position 161, causing the arginine (R) at amino acid position 54 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 16, 2023

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 54 of the NUP107 protein (p.Arg54Gln). This variant is present in population databases (rs139991199, gnomAD 0.08%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with NUP107-related conditions. ClinVar contains an entry for this variant (Variation ID: 2198280). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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

0.099

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

0.023

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.44

M_CAP

Benign

0.036

MetaRNN

Benign

0.034

MetaSVM

Benign

-0.93

PROVEAN

Benign

0.27

REVEL

Benign

0.048

Sift

Benign

0.36

Sift4G

Pathogenic

0.0

Vest4

0.25

MVP

0.57

ClinPred

0.018

GERP RS

5.5

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.35

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.35

Position offset: 26

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over