12-68690492-A-G

Position:

• chr12-68690492-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.188-139A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0259 in 1,070,372 control chromosomes in the GnomAD database, including 494 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.034 (131 hom., cov: 31)
  • Exomes 𝑓: 0.025 (363 hom.)
• Consequence: NUP107 NM_020401.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.200

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=-0.89).
• BP6: Variant 12-68690492-A-G is Benign according to our data. Variant chr12-68690492-A-G is described in ClinVar as [Benign]. Clinvar id is 1271355.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUP107	NM_020401.4	c.188-139A>G		intron_variant		ENST00000229179.9
NUP107	NM_001330192.2	c.73-111A>G		intron_variant
NUP107	XM_005269037.5	c.188-139A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP107	ENST00000229179.9	c.188-139A>G		intron_variant		1	NM_020401.4	P1

Frequencies

GnomAD3 genomes AF: 0.0342 AC: 5207 AN: 152138 Hom.: 131 Cov.: 31

Gnomad AFR AF: 0.0601

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0307

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0398

Gnomad FIN AF: 0.0381

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0231

Gnomad OTH AF: 0.0283

GnomAD4 exome AF: 0.0246 AC: 22547 AN: 918116 Hom.: 363 Cov.: 12 AF XY: 0.0252 AC XY: 11683 AN XY: 462736

Gnomad4 AFR exome AF: 0.0614

Gnomad4 AMR exome AF: 0.0324

Gnomad4 ASJ exome AF: 0.00387

Gnomad4 EAS exome AF: 0.000149

Gnomad4 SAS exome AF: 0.0454

Gnomad4 FIN exome AF: 0.0395

Gnomad4 NFE exome AF: 0.0226

Gnomad4 OTH exome AF: 0.0217

GnomAD4 genome AF: 0.0342 AC: 5212 AN: 152256 Hom.: 131 Cov.: 31 AF XY: 0.0347 AC XY: 2586 AN XY: 74452

Gnomad4 AFR AF: 0.0601

Gnomad4 AMR AF: 0.0306

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.0394

Gnomad4 FIN AF: 0.0381

Gnomad4 NFE AF: 0.0231

Gnomad4 OTH AF: 0.0280

Alfa AF: 0.0329 Hom.: 8

Bravo AF: 0.0330

Asia WGS AF: 0.0190 AC: 66 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

Jan 16, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.6
DANN	Benign	0.68

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: rs71452399; hg19: chr12-69084272;