12-68689457-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.101-76A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 820,098 control chromosomes in the GnomAD database, including 27,514 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (4211 hom., cov: 32)
  • Exomes 𝑓: 0.26 (23303 hom.)
• Consequence: NUP107 NM_020401.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.262

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=-0.91).
• BP6: Variant 12-68689457-A-G is Benign according to our data. Variant chr12-68689457-A-G is described in ClinVar as [Benign]. Clinvar id is 1269304.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUP107	NM_020401.4	c.101-76A>G		intron_variant		ENST00000229179.9
NUP107	NM_001330192.2	c.-15-76A>G		intron_variant
NUP107	XM_005269037.5	c.101-76A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP107	ENST00000229179.9	c.101-76A>G		intron_variant		1	NM_020401.4	P1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 33046 AN: 152030 Hom.: 4209 Cov.: 32

Gnomad AFR AF: 0.0851

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.251

GnomAD4 exome AF: 0.259 AC: 173278 AN: 667950 Hom.: 23303 AF XY: 0.259 AC XY: 91438 AN XY: 353286

Gnomad4 AFR exome AF: 0.0806

Gnomad4 AMR exome AF: 0.277

Gnomad4 ASJ exome AF: 0.252

Gnomad4 EAS exome AF: 0.295

Gnomad4 SAS exome AF: 0.230

Gnomad4 FIN exome AF: 0.271

Gnomad4 NFE exome AF: 0.265

Gnomad4 OTH exome AF: 0.258

GnomAD4 genome AF: 0.217 AC: 33052 AN: 152148 Hom.: 4211 Cov.: 32 AF XY: 0.220 AC XY: 16388 AN XY: 74374

Gnomad4 AFR AF: 0.0851

Gnomad4 AMR AF: 0.264

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.316

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.263

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.254

Alfa AF: 0.248 Hom.: 967

Bravo AF: 0.214

Asia WGS AF: 0.286 AC: 990 AN: 3474

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

Oct 25, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.6
Dann	Benign	0.58

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: rs2546509; hg19: chr12-69083237; COSMIC: COSV57493786; COSMIC: COSV57493786;