rs10497621

Positions:

• chr2-183132715-A-G

Variant summary

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

The ENST00000295119.9(NUP35):​c.340-851A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.054 in 152,320 control chromosomes in the GnomAD database, including 284 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 0.054 (284 hom., cov: 32)
• Consequence: NUP35 ENST00000295119.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43

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=-0.53).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUP35	NM_138285.5	c.340-851A>G		intron_variant		ENST00000295119.9	NP_612142.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUP35	ENST00000295119.9	c.340-851A>G		intron_variant		1	NM_138285.5	ENSP00000295119	P1

Frequencies

GnomAD3 genomes AF: 0.0541 AC: 8235 AN: 152202 Hom.: 284 Cov.: 32

Gnomad AFR AF: 0.0135

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.0644

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0360

Gnomad FIN AF: 0.0568

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0756

Gnomad OTH AF: 0.0611

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0540 AC: 8232 AN: 152320 Hom.: 284 Cov.: 32 AF XY: 0.0540 AC XY: 4023 AN XY: 74480

Gnomad4 AFR AF: 0.0134

Gnomad4 AMR AF: 0.0643

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0360

Gnomad4 FIN AF: 0.0568

Gnomad4 NFE AF: 0.0756

Gnomad4 OTH AF: 0.0605

Alfa AF: 0.0725 Hom.: 251

Bravo AF: 0.0533

Asia WGS AF: 0.0120 AC: 44 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	13
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: rs10497621; hg19: chr2-183997443;