12-68688889-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020401.4(NUP107):c.9-73A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 1,151,510 control chromosomes in the GnomAD database, including 61,816 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.34 (8621 hom., cov: 32)
  • Exomes 𝑓: 0.32 (53195 hom.)
• Consequence: NUP107 NM_020401.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.26

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 12-68688889-A-G is Benign according to our data. Variant chr12-68688889-A-G is described in ClinVar as [Benign]. Clinvar id is 1272631.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUP107	NM_020401.4	c.9-73A>G		intron_variant		ENST00000229179.9
NUP107	NM_001330192.2	c.-107-73A>G		intron_variant
NUP107	XM_005269037.5	c.9-73A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP107	ENST00000229179.9	c.9-73A>G		intron_variant		1	NM_020401.4	P1

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50882 AN: 151854 Hom.: 8613 Cov.: 32

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.366

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.344

GnomAD4 exome AF: 0.325 AC: 324438 AN: 999538 Hom.: 53195 AF XY: 0.324 AC XY: 165376 AN XY: 511022

Gnomad4 AFR exome AF: 0.329

Gnomad4 AMR exome AF: 0.321

Gnomad4 ASJ exome AF: 0.317

Gnomad4 EAS exome AF: 0.282

Gnomad4 SAS exome AF: 0.310

Gnomad4 FIN exome AF: 0.384

Gnomad4 NFE exome AF: 0.324

Gnomad4 OTH exome AF: 0.329

GnomAD4 genome AF: 0.335 AC: 50920 AN: 151972 Hom.: 8621 Cov.: 32 AF XY: 0.339 AC XY: 25169 AN XY: 74256

Gnomad4 AFR AF: 0.335

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.328

Gnomad4 EAS AF: 0.302

Gnomad4 SAS AF: 0.309

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.345

Alfa AF: 0.336 Hom.: 2386

Bravo AF: 0.332

Asia WGS AF: 0.326 AC: 1132 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 20, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.023
Dann	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs2259592; hg19: chr12-69082669; COSMIC: COSV57493562; COSMIC: COSV57493562;