Variant chr5-37294341-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_153485.3(NUP155):c.3918G>C(p.Leu1306Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000279 in 1,434,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

NUP155
NM_153485.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.53

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.846

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUP155	NM_153485.3 link	c.3918G>C	p.Leu1306Phe	missense_variant	33/35	ENST00000231498.8	NP_705618.1	O75694-1A0A024R071
NUP155	NM_004298.4 link	c.3741G>C	p.Leu1247Phe	missense_variant	33/35		NP_004289.1	O75694-2
NUP155	NM_001278312.2 link	c.3726G>C	p.Leu1242Phe	missense_variant	32/34		NP_001265241.1	E9PF10B4DLT2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NUP155	ENST00000231498.8 link	c.3918G>C	p.Leu1306Phe	missense_variant	33/35	1	NM_153485.3	ENSP00000231498.3	O75694-1
NUP155	ENST00000381843.6 link	c.3741G>C	p.Leu1247Phe	missense_variant	33/35	1		ENSP00000371265.2	O75694-2
NUP155	ENST00000513532.1 link	c.3726G>C	p.Leu1242Phe	missense_variant	32/34	1		ENSP00000422019.1	E9PF10
NUP155	ENST00000502533.5 link	n.1576G>C		non_coding_transcript_exon_variant	12/14	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000164

AC:

AN:

243580

Hom.:

AF XY:

0.00000760

AC XY:

AN XY:

131654

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000119

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000279

AC:

AN:

1434462

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

714716

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000910

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

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

Dec 17, 2021

The c.3918G>C (p.L1306F) alteration is located in exon 33 (coding exon 33) of the NUP155 gene. This alteration results from a G to C substitution at nucleotide position 3918, causing the leucine (L) at amino acid position 1306 to be replaced by a phenylalanine (F). 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

Uncertain

0.41

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Pathogenic

0.27

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.73

D;.;T

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.78

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Uncertain

0.15

MetaRNN

Pathogenic

0.85

D;D;D

MetaSVM

Uncertain

-0.0083

MutationAssessor

Uncertain

2.1

M;.;.

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-2.7

D;D;D

REVEL

Pathogenic

0.74

Sift

Uncertain

0.0080

D;D;D

Sift4G

Uncertain

0.022

D;D;D

Polyphen

0.98

D;.;D

Vest4

0.88

MutPred

0.73

Loss of stability (P = 0.0838);.;.;

MVP

0.90

MPC

0.63

ClinPred

0.89

GERP RS

2.9

Varity_R

0.39

gMVP

0.52

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