rs9333281

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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

Gnomad4 AFR exome AF: 0.0180

Gnomad4 AMR exome AF: 0.0769

Gnomad4 ASJ exome AF: 0.0645

Gnomad4 EAS exome AF: 0.0935

Gnomad4 SAS exome AF: 0.142

Gnomad4 FIN exome AF: 0.0380

Gnomad4 NFE exome AF: 0.0440

Gnomad4 OTH exome AF: 0.0564

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

Gnomad4 AFR AF: 0.0183

Gnomad4 AMR AF: 0.0595

Gnomad4 ASJ AF: 0.0674

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.0328

Gnomad4 NFE AF: 0.0493

Gnomad4 OTH AF: 0.0470

Alfa AF: 0.0438 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

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: rs9333281; hg19: chr2-183995075;