rs768431722

Variant names:

• chr5-37294330-C-A
• rs768431722
• NM_153485.3:c.3929G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-37294330-C-A
• chr5-37294330-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_153485.3(NUP155):​c.3929G>T​(p.Arg1310Leu) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000212 in 1,412,312 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: NUP155 NM_153485.3 missense, splice_region
• Scores: Splicing: ADA: 0.9904
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.26

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.828

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUP155	NM_153485.3	c.3929G>T	p.Arg1310Leu	missense_variant, splice_region_variant	Exon 33 of 35	ENST00000231498.8	NP_705618.1
NUP155	NM_004298.4	c.3752G>T	p.Arg1251Leu	missense_variant, splice_region_variant	Exon 33 of 35		NP_004289.1
NUP155	NM_001278312.2	c.3737G>T	p.Arg1246Leu	missense_variant, splice_region_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.3929G>T	p.Arg1310Leu	missense_variant, splice_region_variant	Exon 33 of 35	1	NM_153485.3	ENSP00000231498.3
NUP155	ENST00000381843.6	c.3752G>T	p.Arg1251Leu	missense_variant, splice_region_variant	Exon 33 of 35	1		ENSP00000371265.2
NUP155	ENST00000513532.1	c.3737G>T	p.Arg1246Leu	missense_variant, splice_region_variant	Exon 32 of 34	1		ENSP00000422019.1
NUP155	ENST00000502533.5	n.1587G>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 12 of 14	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000430 AC: 1 AN: 232806 Hom.: 0 AF XY: 0.00000795 AC XY: 1 AN XY: 125810

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: 0.0000346

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000212 AC: 3 AN: 1412312 Hom.: 0 Cov.: 26 AF XY: 0.00000142 AC XY: 1 AN XY: 703818

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000360

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.25
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.63	D;.;T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.83	D;D;D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Benign	1.8	L;.;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-3.3	D;D;D
REVEL	Pathogenic	0.70
Sift	Benign	0.093	T;T;T
Sift4G	Uncertain	0.042	D;D;D
Polyphen		0.84	P;.;D
Vest4		0.90
MutPred		0.65		Loss of solvent accessibility (P = 0.0442);.;.;
MVP		0.57
MPC		0.20
ClinPred		0.81	D
GERP RS		5.8
Varity_R		0.29
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.99
dbscSNV1_RF	Pathogenic	0.82
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: rs768431722; hg19: chr5-37294432;