5-37294341-C-G

Variant summary

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

The NM_153485.3(NUP155):ā€‹c.3918G>Cā€‹(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 (ā˜…). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes š‘“: 0.0000028 ( 0 hom. )

Consequence

NUP155
NM_153485.3 missense

Scores

4
14
1

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]

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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 UniProt
NUP155NM_153485.3 linkuse as main transcriptc.3918G>C p.Leu1306Phe missense_variant 33/35 ENST00000231498.8
NUP155NM_004298.4 linkuse as main transcriptc.3741G>C p.Leu1247Phe missense_variant 33/35
NUP155NM_001278312.2 linkuse as main transcriptc.3726G>C p.Leu1242Phe missense_variant 32/34

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NUP155ENST00000231498.8 linkuse as main transcriptc.3918G>C p.Leu1306Phe missense_variant 33/351 NM_153485.3 P1O75694-1
NUP155ENST00000381843.6 linkuse as main transcriptc.3741G>C p.Leu1247Phe missense_variant 33/351 O75694-2
NUP155ENST00000513532.1 linkuse as main transcriptc.3726G>C p.Leu1242Phe missense_variant 32/341
NUP155ENST00000502533.5 linkuse as main transcriptn.1576G>C non_coding_transcript_exon_variant 12/145

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.0000164
AC:
4
AN:
243580
Hom.:
0
AF XY:
0.00000760
AC XY:
1
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:
4
AN:
1434462
Hom.:
0
Cov.:
27
AF XY:
0.00000140
AC XY:
1
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.:
31
ExAC
AF:
0.0000165
AC:
2

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 submitterclinical testingAmbry GeneticsDec 17, 2021The 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
D
BayesDel_noAF
Pathogenic
0.27
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.73
D;.;T
Eigen
Uncertain
0.36
Eigen_PC
Uncertain
0.32
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Uncertain
0.93
D;D;D
M_CAP
Uncertain
0.15
D
MetaRNN
Pathogenic
0.85
D;D;D
MetaSVM
Uncertain
-0.0083
T
MutationAssessor
Uncertain
2.1
M;.;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.72
T
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
D
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.

Other links and lift over

dbSNP: rs774178827; hg19: chr5-37294443; API