rs3214915

Variant names:

• chr17-75234841-TTA-T
• rs3214915
• NM_024844.5:c.1767+54_1767+55delTA

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

NUP85 Gene-Disease associations (from GenCC):

• nephrotic syndrome, type 17

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NUP85	NM_024844.5	c.1767+54_1767+55delTA		intron_variant	Intron 17 of 18	ENST00000245544.9	NP_079120.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUP85	ENST00000245544.9	c.1767+54_1767+55delTA		intron_variant	Intron 17 of 18	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

GnomAD2 exomes AF: 0.0362 AC: 9057 AN: 250348 AF XY: 0.0336

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 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

African (AFR) AF: 0.206 AC: 6860 AN: 33302

American (AMR) AF: 0.0508 AC: 2271 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00529 AC: 138 AN: 26078

East Asian (EAS) AF: 0.0611 AC: 2422 AN: 39664

South Asian (SAS) AF: 0.0764 AC: 6572 AN: 86060

European-Finnish (FIN) AF: 0.0000191 AC: 1 AN: 52478

Middle Eastern (MID) AF: 0.0268 AC: 154 AN: 5754

European-Non Finnish (NFE) AF: 0.00116 AC: 1276 AN: 1102978

Other (OTH) AF: 0.0265 AC: 1589 AN: 60054

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

African (AFR) AF: 0.194 AC: 8045 AN: 41470

American (AMR) AF: 0.0644 AC: 985 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00404 AC: 14 AN: 3466

East Asian (EAS) AF: 0.0760 AC: 394 AN: 5184

South Asian (SAS) AF: 0.0826 AC: 399 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.00166 AC: 113 AN: 68018

Other (OTH) AF: 0.0617 AC: 130 AN: 2108

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

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.11
Mutation Taster		=164/36	polymorphism (auto)

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

Other links and lift over

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