5-37294330-C-T

Position:

chr5-37294330-C-T

Variant summary

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

The NM_153485.3(NUP155):c.3929G>A(p.Arg1310Gln) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000895 in 1,564,264 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000078 ( 0 hom. )

Consequence

NUP155
NM_153485.3 missense, splice_region

Scores

Splicing: ADA: 0.9584

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.26

Variant links:

Genes affected

NUP155 (HGNC:8063): (nucleoporin 155) Nucleoporins are proteins that play an important role in the assembly and functioning of the nuclear pore complex (NPC) which regulates the movement of macromolecules across the nuclear envelope (NE). The protein encoded by this gene plays a role in the fusion of NE vesicles and formation of the double membrane NE. The protein may also be involved in cardiac physiology and may be associated with the pathogenesis of atrial fibrillation. Alternative splicing results in multiple transcript variants of this gene. A pseudogene associated with this gene is located on chromosome 6. [provided by RefSeq, May 2013]

NUP155 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
NUP155	NM_153485.3 linkuse as main transcript	c.3929G>A	p.Arg1310Gln	missense_variant, splice_region_variant	33/35	ENST00000231498.8
NUP155	NM_004298.4 linkuse as main transcript	c.3752G>A	p.Arg1251Gln	missense_variant, splice_region_variant	33/35
NUP155	NM_001278312.2 linkuse as main transcript	c.3737G>A	p.Arg1246Gln	missense_variant, splice_region_variant	32/34

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP155	ENST00000231498.8 linkuse as main transcript	c.3929G>A	p.Arg1310Gln	missense_variant, splice_region_variant	33/35	1	NM_153485.3	P1	O75694-1
NUP155	ENST00000381843.6 linkuse as main transcript	c.3752G>A	p.Arg1251Gln	missense_variant, splice_region_variant	33/35	1			O75694-2
NUP155	ENST00000513532.1 linkuse as main transcript	c.3737G>A	p.Arg1246Gln	missense_variant, splice_region_variant	32/34	1
NUP155	ENST00000502533.5 linkuse as main transcript	n.1587G>A		splice_region_variant, non_coding_transcript_exon_variant	12/14	5

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

151952

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000129

AC:

AN:

232806

Hom.:

AF XY:

0.0000159

AC XY:

AN XY:

125810

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000575

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000194

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000779

AC:

AN:

1412312

Hom.:

Cov.:

AF XY:

0.00000995

AC XY:

AN XY:

703818

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.0000240

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000653

Gnomad4 OTH exome

AF:

0.0000171

GnomAD4 genome

AF:

0.0000197

AC:

AN:

151952

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74194

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000772

Hom.:

Bravo

AF:

0.0000264

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

May 14, 2024

The c.3929G>A (p.R1310Q) alteration is located in exon 33 (coding exon 33) of the NUP155 gene. This alteration results from a G to A substitution at nucleotide position 3929, causing the arginine (R) at amino acid position 1310 to be replaced by a glutamine (Q). 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

Benign

0.33

BayesDel_addAF

Uncertain

0.071

BayesDel_noAF

Uncertain

0.040

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;.;T

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Benign

0.052

MetaRNN

Uncertain

0.57

D;D;D

MetaSVM

Benign

-0.58

MutationAssessor

Benign

1.8

L;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.0

N;N;N

REVEL

Uncertain

0.43

Sift

Benign

0.20

T;T;T

Sift4G

Benign

0.092

T;T;T

Polyphen

0.85

P;.;D

Vest4

0.63

MVP

0.66

MPC

0.16

ClinPred

0.54

GERP RS

5.8

Varity_R

0.18

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.96

dbscSNV1_RF

Benign

0.67

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