5-37294371-T-A

Variant names:

• chr5-37294371-T-A
• rs1045908
• NM_153485.3:c.3888A>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_153485.3(NUP155):​c.3888A>T​(p.Leu1296Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
• Consequence: NUP155 NM_153485.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.851

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUP155	NM_153485.3	c.3888A>T	p.Leu1296Phe	missense_variant	Exon 33 of 35	ENST00000231498.8	NP_705618.1
NUP155	NM_004298.4	c.3711A>T	p.Leu1237Phe	missense_variant	Exon 33 of 35		NP_004289.1
NUP155	NM_001278312.2	c.3696A>T	p.Leu1232Phe	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.3888A>T	p.Leu1296Phe	missense_variant	Exon 33 of 35	1	NM_153485.3	ENSP00000231498.3
NUP155	ENST00000381843.6	c.3711A>T	p.Leu1237Phe	missense_variant	Exon 33 of 35	1		ENSP00000371265.2
NUP155	ENST00000513532.1	c.3696A>T	p.Leu1232Phe	missense_variant	Exon 32 of 34	1		ENSP00000422019.1
NUP155	ENST00000502533.5	n.1546A>T		non_coding_transcript_exon_variant	Exon 12 of 14	5

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152002 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 249696 Hom.: 0 AF XY: 0.00000741 AC XY: 1 AN XY: 134980

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000328

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152002 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74228

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	0.0069	T
BayesDel_noAF	Benign	-0.13
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T;.;T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.29
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Benign	0.020	T
MetaRNN	Pathogenic	0.85	D;D;D
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.4	L;.;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Uncertain	0.34
Sift	Benign	0.18	T;T;T
Sift4G	Benign	0.72	T;T;T
Polyphen		0.021	B;.;B
Vest4		0.66
MutPred		0.69		Loss of helix (P = 0.2271);.;.;
MVP		0.81
MPC		0.16
ClinPred		0.26	T
GERP RS		1.6
Varity_R		0.072
gMVP		0.38

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

Other links and lift over

dbSNP: rs1045908; hg19: chr5-37294473;