Genetic Variant NUP35:c.212-4G>A (chr2-183130414-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_138285.5(NUP35):c.212-4G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000469 in 1,322,638 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000068 ( 0 hom., cov: 25)

Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

NUP35
NM_138285.5 splice_region, intron

Scores

Splicing: ADA: 0.00003898

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.250

Publications

3 publications found

Variant links:

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]

NUP35 links:

ENSG00000224643 (HGNC:):

ENSG00000224643 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUP35	NM_138285.5 link	c.212-4G>A		splice_region_variant, intron_variant	Intron 2 of 8	ENST00000295119.9	NP_612142.2	Q8NFH5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUP35	ENST00000295119.9 link	c.212-4G>A		splice_region_variant, intron_variant	Intron 2 of 8	1	NM_138285.5	ENSP00000295119.4		Q8NFH5-1

Frequencies

GnomAD3 genomes

AF:

0.0000677

AC:

AN:

103350

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000121

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00152

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000812

AC:

AN:

221758

AF XY:

0.0000663

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00112

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000451

AC:

AN:

1219272

Hom.:

Cov.:

AF XY:

0.0000343

AC XY:

AN XY:

612468

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26112

American (AMR)

AF:

0.00

AC:

AN:

37228

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22640

East Asian (EAS)

AF:

0.00144

AC:

AN:

35506

South Asian (SAS)

AF:

0.0000265

AC:

AN:

75456

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49648

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3812

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

917900

Other (OTH)

AF:

0.0000392

AC:

AN:

50970

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000677

AC:

AN:

103366

Hom.:

Cov.:

AF XY:

0.0000835

AC XY:

AN XY:

47916

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24834

American (AMR)

AF:

0.000121

AC:

AN:

8264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2962

East Asian (EAS)

AF:

0.00153

AC:

AN:

3928

South Asian (SAS)

AF:

0.00

AC:

AN:

3726

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3768

Middle Eastern (MID)

AF:

0.00

AC:

AN:

132

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53650

Other (OTH)

AF:

0.00

AC:

AN:

1396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

2.8

(source)

DANN

Benign

0.39

PhyloP100

-0.25

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000039

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over