5-37294457-C-T

Variant names:

• chr5-37294457-C-T
• NM_153485.3:c.3802G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153485.3(NUP155):​c.3802G>A​(p.Val1268Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: NUP155 NM_153485.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.49

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1191065).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUP155	NM_153485.3	c.3802G>A	p.Val1268Ile	missense_variant	Exon 33 of 35	ENST00000231498.8	NP_705618.1
NUP155	NM_004298.4	c.3625G>A	p.Val1209Ile	missense_variant	Exon 33 of 35		NP_004289.1
NUP155	NM_001278312.2	c.3610G>A	p.Val1204Ile	missense_variant	Exon 32 of 34		NP_001265241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUP155	ENST00000231498.8	c.3802G>A	p.Val1268Ile	missense_variant	Exon 33 of 35	1	NM_153485.3	ENSP00000231498.3
NUP155	ENST00000381843.6	c.3625G>A	p.Val1209Ile	missense_variant	Exon 33 of 35	1		ENSP00000371265.2
NUP155	ENST00000513532.1	c.3610G>A	p.Val1204Ile	missense_variant	Exon 32 of 34	1		ENSP00000422019.1
NUP155	ENST00000502533.5	n.1460G>A		non_coding_transcript_exon_variant	Exon 12 of 14	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 13, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3802G>A (p.V1268I) 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 3802, causing the valine (V) at amino acid position 1268 to be replaced by an isoleucine (I). 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	0.076
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	17
DANN	Benign	0.90
DEOGEN2	Benign	0.12	T;.;T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.39
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.79	T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.5	L;.;.
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.45	N;N;N
REVEL	Benign	0.22
Sift	Benign	0.19	T;T;T
Sift4G	Benign	0.25	T;T;T
Polyphen		0.0010	B;.;B
Vest4		0.12
MutPred		0.50		Loss of catalytic residue at V1268 (P = 0.111);.;.;
MVP		0.14
MPC		0.13
ClinPred		0.52	D
GERP RS		3.1
Varity_R		0.043
gMVP		0.28

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-37294559;