12-68688870-CT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_020401.4(NUP107):c.9-91del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0272 in 886,082 control chromosomes in the GnomAD database, including 427 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.030 (91 hom., cov: 32)
  • Exomes 𝑓: 0.027 (336 hom.)
• Consequence: NUP107 NM_020401.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.546

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 -10 ACMG points.

• BP6: Variant 12-68688870-CT-C is Benign according to our data. Variant chr12-68688870-CT-C is described in ClinVar as [Likely_benign]. Clinvar id is 1201224.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0303 (4613/152256) while in subpopulation AFR AF= 0.0462 (1919/41546). AF 95% confidence interval is 0.0445. There are 91 homozygotes in gnomad4. There are 2294 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 91 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUP107	NM_020401.4	c.9-91del		intron_variant		ENST00000229179.9
NUP107	NM_001330192.2	c.-107-91del		intron_variant
NUP107	XM_005269037.5	c.9-91del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP107	ENST00000229179.9	c.9-91del		intron_variant		1	NM_020401.4	P1

Frequencies

GnomAD3 genomes AF: 0.0303 AC: 4614 AN: 152138 Hom.: 91 Cov.: 32

Gnomad AFR AF: 0.0463

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0298

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0404

Gnomad FIN AF: 0.0377

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0231

Gnomad OTH AF: 0.0264

GnomAD4 exome AF: 0.0266 AC: 19484 AN: 733826 Hom.: 336 AF XY: 0.0271 AC XY: 10332 AN XY: 381306

Gnomad4 AFR exome AF: 0.0475

Gnomad4 AMR exome AF: 0.0319

Gnomad4 ASJ exome AF: 0.00424

Gnomad4 EAS exome AF: 0.000183

Gnomad4 SAS exome AF: 0.0461

Gnomad4 FIN exome AF: 0.0403

Gnomad4 NFE exome AF: 0.0250

Gnomad4 OTH exome AF: 0.0219

GnomAD4 genome AF: 0.0303 AC: 4613 AN: 152256 Hom.: 91 Cov.: 32 AF XY: 0.0308 AC XY: 2294 AN XY: 74438

Gnomad4 AFR AF: 0.0462

Gnomad4 AMR AF: 0.0297

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0400

Gnomad4 FIN AF: 0.0377

Gnomad4 NFE AF: 0.0231

Gnomad4 OTH AF: 0.0261

Alfa AF: 0.0114 Hom.: 2

Bravo AF: 0.0285

Asia WGS AF: 0.0170 AC: 60 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 16, 2020

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Computational scores

Source: dbNSFP v4.3

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: rs35079356; hg19: chr12-69082650;