Variant 2-183158407-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_138285.5(NUP35):c.734A>C(p.Asp245Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000352 in 1,597,644 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00037 ( 0 hom. )

Consequence

NUP35
NM_138285.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.94

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUP35	NM_138285.5 linkuse as main transcript	c.734A>C	p.Asp245Ala	missense_variant	7/9	ENST00000295119.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP35	ENST00000295119.9 linkuse as main transcript	c.734A>C	p.Asp245Ala	missense_variant	7/9	1	NM_138285.5	P1	Q8NFH5-1
NUP35	ENST00000409798.5 linkuse as main transcript	c.683A>C	p.Asp228Ala	missense_variant	8/10	2			Q8NFH5-2
NUP35	ENST00000479162.5 linkuse as main transcript	n.631A>C		non_coding_transcript_exon_variant	6/7	2
NUP35	ENST00000374930.7 linkuse as main transcript	c.*133A>C		3_prime_UTR_variant, NMD_transcript_variant	6/8	2

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000470

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000194

AC:

AN:

242694

Hom.:

AF XY:

0.000175

AC XY:

AN XY:

131206

show subpopulations

Gnomad AFR exome

AF:

0.0000625

Gnomad AMR exome

AF:

0.0000938

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000378

Gnomad OTH exome

AF:

0.000170

GnomAD4 exome

AF:

0.000365

AC:

528

AN:

1445458

Hom.:

Cov.:

AF XY:

0.000355

AC XY:

255

AN XY:

718624

show subpopulations

Gnomad4 AFR exome

AF:

0.0000302

Gnomad4 AMR exome

AF:

0.0000698

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.000460

Gnomad4 OTH exome

AF:

0.000268

GnomAD4 genome

AF:

0.000230

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000470

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000470

Hom.:

Bravo

AF:

0.000272

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000214

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 12, 2022

The c.734A>C (p.D245A) alteration is located in exon 7 (coding exon 7) of the NUP35 gene. This alteration results from a A to C substitution at nucleotide position 734, causing the aspartic acid (D) at amino acid position 245 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.84

BayesDel_addAF

Uncertain

0.056

BayesDel_noAF

Pathogenic

0.16

Cadd

Pathogenic

Dann

Uncertain

1.0

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

D;D

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.69

D;D

MetaSVM

Benign

-0.29

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.75

PROVEAN

Pathogenic

-5.9

D;D

REVEL

Uncertain

0.58

Sift

Uncertain

0.0050

D;D

Sift4G

Uncertain

0.0090

D;D

Polyphen

0.98

.;D

Vest4

0.69

MVP

0.78

MPC

0.84

ClinPred

0.67

GERP RS

5.8

Varity_R

0.69

gMVP

0.69

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over