5-37298882-C-G

Variant names:

• chr5-37298882-C-G
• rs142078226
• NM_153485.3:c.3779G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_153485.3(NUP155):​c.3779G>C​(p.Arg1260Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1260H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NUP155 NM_153485.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.26
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.824

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.3779G>C	p.Arg1260Pro	missense	Exon 32 of 35	NP_705618.1	O75694-1
	NUP155	NM_004298.4		c.3602G>C	p.Arg1201Pro	missense	Exon 32 of 35	NP_004289.1	O75694-2
	NUP155	NM_001278312.2		c.3587G>C	p.Arg1196Pro	missense	Exon 31 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.3779G>C	p.Arg1260Pro	missense	Exon 32 of 35	ENSP00000231498.3	O75694-1
	NUP155	ENST00000381843.6	TSL:1	c.3602G>C	p.Arg1201Pro	missense	Exon 32 of 35	ENSP00000371265.2	O75694-2
	NUP155	ENST00000513532.1	TSL:1	c.3587G>C	p.Arg1196Pro	missense	Exon 31 of 34	ENSP00000422019.1	E9PF10

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.59	D
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.066	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.45	T
MutationAssessor	Benign	1.6	L
PhyloP100		7.3
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.59
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.019	D
Polyphen		0.41	B
Vest4		0.90
MutPred		0.62		Gain of glycosylation at R1260 (P = 0.0312)
MVP		0.79
MPC		0.75
ClinPred		0.98	D
GERP RS		5.8
Varity_R		0.68
gMVP		0.84
Mutation Taster		=50/50

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

dbSNP: rs142078226; hg19: chr5-37298984;