2-183130414-G-T

Variant names:

• chr2-183130414-G-T
• rs9333283
• NM_138285.5:c.212-4G>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138285.5(NUP35):​c.212-4G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0648 in 1,320,294 control chromosomes in the GnomAD database, including 3,053 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.067 (253 hom., cov: 25)
  • Exomes 𝑓: 0.065 (2800 hom.)
• Consequence: NUP35 NM_138285.5 splice_region, intron
• Scores: Splicing: ADA: 0.00001930
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.250

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=-0.6).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUP35	NM_138285.5	c.212-4G>T		splice_region_variant, 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.212-4G>T		splice_region_variant, intron_variant	Intron 2 of 8	1	NM_138285.5	ENSP00000295119.4

Frequencies

GnomAD3 genomes AF: 0.0672 AC: 6927 AN: 103106 Hom.: 253 Cov.: 25

Gnomad AFR AF: 0.0299

Gnomad AMI AF: 0.00994

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.0790

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.0858

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.0622

Gnomad OTH AF: 0.0690

GnomAD3 exomes AF: 0.0670 AC: 14859 AN: 221758 Hom.: 709 AF XY: 0.0691 AC XY: 8337 AN XY: 120696

Gnomad AFR exome AF: 0.0183

Gnomad AMR exome AF: 0.0766

Gnomad ASJ exome AF: 0.0691

Gnomad EAS exome AF: 0.112

Gnomad SAS exome AF: 0.142

Gnomad FIN exome AF: 0.0377

Gnomad NFE exome AF: 0.0511

Gnomad OTH exome AF: 0.0602

GnomAD4 exome AF: 0.0646 AC: 78645 AN: 1217172 Hom.: 2800 Cov.: 32 AF XY: 0.0671 AC XY: 41049 AN XY: 611518

Gnomad4 AFR exome AF: 0.0235

Gnomad4 AMR exome AF: 0.0810

Gnomad4 ASJ exome AF: 0.0706

Gnomad4 EAS exome AF: 0.103

Gnomad4 SAS exome AF: 0.151

Gnomad4 FIN exome AF: 0.0396

Gnomad4 NFE exome AF: 0.0573

Gnomad4 OTH exome AF: 0.0687

GnomAD4 genome AF: 0.0672 AC: 6928 AN: 103122 Hom.: 253 Cov.: 25 AF XY: 0.0722 AC XY: 3448 AN XY: 47786

Gnomad4 AFR AF: 0.0300

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.0790

Gnomad4 EAS AF: 0.136

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.0858

Gnomad4 NFE AF: 0.0622

Gnomad4 OTH AF: 0.0700

Alfa AF: 0.0378 Hom.: 64

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	2.3
DANN	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000019
dbscSNV1_RF	Benign	0.0020
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: rs9333283; hg19: chr2-183995142;