12-68689014-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020401.4(NUP107):c.61C>T(p.Arg21Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000446 in 1,613,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R21Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000040 (0 hom.)
• Consequence: NUP107 NM_020401.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 0.147

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21016037).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUP107	NM_020401.4	c.61C>T	p.Arg21Trp	missense_variant	2/28	ENST00000229179.9
NUP107	XM_005269037.5	c.61C>T	p.Arg21Trp	missense_variant	2/27
NUP107	NM_001330192.2	c.-55C>T		5_prime_UTR_variant	2/28

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP107	ENST00000229179.9	c.61C>T	p.Arg21Trp	missense_variant	2/28	1	NM_020401.4	P1

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152126 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.0000597 AC: 15 AN: 251102 Hom.: 0 AF XY: 0.0000590 AC XY: 8 AN XY: 135706

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000654

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.0000397 AC: 58 AN: 1461316 Hom.: 0 Cov.: 29 AF XY: 0.0000426 AC XY: 31 AN XY: 726972

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.000201

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000315

Gnomad4 OTH exome AF: 0.0000828

GnomAD4 genome AF: 0.0000920 AC: 14 AN: 152244 Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10 AN XY: 74420

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.0000422 Hom.: 0

Bravo AF: 0.0000869

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000412 AC: 5

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 17, 2022

The c.61C>T (p.R21W) alteration is located in exon 2 (coding exon 2) of the NUP107 gene. This alteration results from a C to T substitution at nucleotide position 61, causing the arginine (R) at amino acid position 21 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Premature ovarian insufficiency Uncertain:1

Uncertain significance, no assertion criteria provided

research

Reproductive Development, Murdoch Childrens Research Institute

Jan 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Uncertain	-0.040
Cadd	Benign	23
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.0096
Eigen_PC	Benign	-0.074
FATHMM_MKL	Benign	0.14	N
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	2.0	M
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.47
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.23
MVP		0.66
MPC		0.26
ClinPred		0.79	D
GERP RS		2.3
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.11
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs139309724; hg19: chr12-69082794;