17-75234841-TTA-T

Position:

• chr17-75234841-TTA-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_024844.5(NUP85):​c.1767+54_1767+55delTA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0196 in 1,603,254 control chromosomes in the GnomAD database, including 2,189 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.066 (907 hom., cov: 32)
  • Exomes 𝑓: 0.015 (1282 hom.)
• Consequence: NUP85 NM_024844.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.113

Genes affected

NUP85 (HGNC:8734): (nucleoporin 85) This gene encodes a protein component of the Nup107-160 subunit of the nuclear pore complex. Nuclear pore complexes are embedded in the nuclear envelope and promote bidirectional transport of macromolecules between the cytoplasm and nucleus. The encoded protein can also bind to the C-terminus of chemokine (C-C motif) receptor 2 (CCR2) and promote chemotaxis of monocytes, thereby participating in the inflammatory response. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUP85	NM_024844.5	c.1767+54_1767+55delTA		intron_variant		ENST00000245544.9	NP_079120.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUP85	ENST00000245544.9	c.1767+54_1767+55delTA		intron_variant		1	NM_024844.5	ENSP00000245544.4

Frequencies

GnomAD3 genomes AF: 0.0662 AC: 10074 AN: 152064 Hom.: 901 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0646

Gnomad ASJ AF: 0.00404

Gnomad EAS AF: 0.0758

Gnomad SAS AF: 0.0833

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.00166

Gnomad OTH AF: 0.0623

GnomAD3 exomes AF: 0.0362 AC: 9057 AN: 250348 Hom.: 593 AF XY: 0.0336 AC XY: 4549 AN XY: 135386

Gnomad AFR exome AF: 0.199

Gnomad AMR exome AF: 0.0488

Gnomad ASJ exome AF: 0.00566

Gnomad EAS exome AF: 0.0718

Gnomad SAS exome AF: 0.0796

Gnomad FIN exome AF: 0.0000478

Gnomad NFE exome AF: 0.00183

Gnomad OTH exome AF: 0.0193

GnomAD4 exome AF: 0.0147 AC: 21283 AN: 1451072 Hom.: 1282 AF XY: 0.0157 AC XY: 11368 AN XY: 722612

Gnomad4 AFR exome AF: 0.206

Gnomad4 AMR exome AF: 0.0508

Gnomad4 ASJ exome AF: 0.00529

Gnomad4 EAS exome AF: 0.0611

Gnomad4 SAS exome AF: 0.0764

Gnomad4 FIN exome AF: 0.0000191

Gnomad4 NFE exome AF: 0.00116

Gnomad4 OTH exome AF: 0.0265

GnomAD4 genome AF: 0.0663 AC: 10092 AN: 152182 Hom.: 907 Cov.: 32 AF XY: 0.0666 AC XY: 4957 AN XY: 74404

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.0644

Gnomad4 ASJ AF: 0.00404

Gnomad4 EAS AF: 0.0760

Gnomad4 SAS AF: 0.0826

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00166

Gnomad4 OTH AF: 0.0617

Alfa AF: 0.0266 Hom.: 57

Bravo AF: 0.0744

Asia WGS AF: 0.0980 AC: 342 AN: 3478

EpiCase AF: 0.00251

EpiControl AF: 0.00196

ClinVar

Not reported in ClinVar

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: rs3214915; hg19: chr17-73230936; COSMIC: COSV55456455; COSMIC: COSV55456455;