5-37294457-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 16/22 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
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• familial atrial fibrillation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• atrial fibrillation, familial, 15

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153485.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP155	NM_153485.3	MANE Select	c.3802G>A	p.Val1268Ile	missense	Exon 33 of 35	NP_705618.1	O75694-1
	NUP155	NM_004298.4		c.3625G>A	p.Val1209Ile	missense	Exon 33 of 35	NP_004289.1	O75694-2
	NUP155	NM_001278312.2		c.3610G>A	p.Val1204Ile	missense	Exon 32 of 34	NP_001265241.1	E9PF10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP155	ENST00000231498.8	TSL:1 MANE Select	c.3802G>A	p.Val1268Ile	missense	Exon 33 of 35	ENSP00000231498.3	O75694-1
	NUP155	ENST00000381843.6	TSL:1	c.3625G>A	p.Val1209Ile	missense	Exon 33 of 35	ENSP00000371265.2	O75694-2
	NUP155	ENST00000513532.1	TSL:1	c.3610G>A	p.Val1204Ile	missense	Exon 32 of 34	ENSP00000422019.1	E9PF10

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.39
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.5	L
PhyloP100		4.5
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.22
Sift	Benign	0.19	T
Sift4G	Benign	0.25	T
Polyphen		0.0010	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
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

hg19: chr5-37294559;