rs9333281

Variant names:

• chr2-183130347-A-G
• rs9333281
• NM_138285.5:c.212-71A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138285.5(NUP35):​c.212-71A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0506 in 1,455,488 control chromosomes in the GnomAD database, including 2,426 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.046 (246 hom., cov: 32)
  • Exomes 𝑓: 0.051 (2180 hom.)
• Consequence: NUP35 NM_138285.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.462
• Publications: 1 publications found

Genes affected

NUP35 (HGNC:29797): (nucleoporin 35) This gene encodes a member of the nucleoporin family. The encoded protein contains two membrane binding regions, is localized to the nuclear rim, and is part of the nuclear pore complex. All molecules entering or leaving the nucleus either diffuse through or are actively transported by the nuclear pore complex. Alternative splicing results in multiple transcript variants. Pseudogenes of this gene have been defined on chromosomes 7 and 10. [provided by RefSeq, Dec 2013]

ENSG00000224643 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUP35	NM_138285.5	c.212-71A>G		intron_variant	Intron 2 of 8	ENST00000295119.9	NP_612142.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUP35	ENST00000295119.9	c.212-71A>G		intron_variant	Intron 2 of 8	1	NM_138285.5	ENSP00000295119.4

Frequencies

GnomAD3 genomes AF: 0.0461 AC: 7009 AN: 151990 Hom.: 246 Cov.: 32

Gnomad AFR AF: 0.0183

Gnomad AMI AF: 0.00771

Gnomad AMR AF: 0.0597

Gnomad ASJ AF: 0.0674

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.0328

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0492

Gnomad OTH AF: 0.0465

GnomAD4 exome AF: 0.0512 AC: 66673 AN: 1303380 Hom.: 2180 AF XY: 0.0540 AC XY: 34764 AN XY: 643504

African (AFR) AF: 0.0180 AC: 496 AN: 27600

American (AMR) AF: 0.0769 AC: 2107 AN: 27410

Ashkenazi Jewish (ASJ) AF: 0.0645 AC: 1295 AN: 20074

East Asian (EAS) AF: 0.0935 AC: 3398 AN: 36358

South Asian (SAS) AF: 0.142 AC: 9247 AN: 65252

European-Finnish (FIN) AF: 0.0380 AC: 1783 AN: 46966

Middle Eastern (MID) AF: 0.0943 AC: 337 AN: 3574

European-Non Finnish (NFE) AF: 0.0440 AC: 44977 AN: 1022410

Other (OTH) AF: 0.0564 AC: 3033 AN: 53736

GnomAD4 genome AF: 0.0461 AC: 7011 AN: 152108 Hom.: 246 Cov.: 32 AF XY: 0.0470 AC XY: 3497 AN XY: 74364

African (AFR) AF: 0.0183 AC: 760 AN: 41498

American (AMR) AF: 0.0595 AC: 908 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0674 AC: 234 AN: 3472

East Asian (EAS) AF: 0.104 AC: 536 AN: 5158

South Asian (SAS) AF: 0.154 AC: 741 AN: 4822

European-Finnish (FIN) AF: 0.0328 AC: 347 AN: 10576

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0493 AC: 3351 AN: 68012

Other (OTH) AF: 0.0470 AC: 99 AN: 2108

Alfa AF: 0.0428 Hom.: 16

Bravo AF: 0.0458

Asia WGS AF: 0.119 AC: 412 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.2
DANN	Benign	0.79
PhyloP100		0.46
Mutation Taster		=100/0	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: rs9333281; hg19: chr2-183995075;