5-37350288-C-A

Variant names:

• chr5-37350288-C-A
• rs217776
• NM_153485.3:c.724-23G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_153485.3(NUP155):​c.724-23G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,524,262 control chromosomes in the GnomAD database, including 39,416 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (12380 hom., cov: 32)
  • Exomes 𝑓: 0.18 (27036 hom.)
• Consequence: NUP155 NM_153485.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.315
• Publications: 3 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: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 5-37350288-C-A is Benign according to our data. Variant chr5-37350288-C-A is described in ClinVar as Benign. ClinVar VariationId is 1180263.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUP155	NM_153485.3	c.724-23G>T		intron_variant	Intron 6 of 34	ENST00000231498.8	NP_705618.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUP155	ENST00000231498.8	c.724-23G>T		intron_variant	Intron 6 of 34	1	NM_153485.3	ENSP00000231498.3

Frequencies

GnomAD3 genomes AF: 0.323 AC: 48985 AN: 151860 Hom.: 12343 Cov.: 32

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.291

GnomAD2 exomes AF: 0.215 AC: 53837 AN: 250426 AF XY: 0.204

Gnomad AFR exome AF: 0.716

Gnomad AMR exome AF: 0.228

Gnomad ASJ exome AF: 0.183

Gnomad EAS exome AF: 0.116

Gnomad FIN exome AF: 0.206

Gnomad NFE exome AF: 0.162

Gnomad OTH exome AF: 0.190

GnomAD4 exome AF: 0.176 AC: 241335 AN: 1372284 Hom.: 27036 Cov.: 22 AF XY: 0.176 AC XY: 120756 AN XY: 687612

African (AFR) AF: 0.725 AC: 23068 AN: 31806

American (AMR) AF: 0.227 AC: 10090 AN: 44486

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 4667 AN: 25544

East Asian (EAS) AF: 0.0982 AC: 3849 AN: 39180

South Asian (SAS) AF: 0.208 AC: 17475 AN: 84172

European-Finnish (FIN) AF: 0.201 AC: 10708 AN: 53254

Middle Eastern (MID) AF: 0.193 AC: 1077 AN: 5590

European-Non Finnish (NFE) AF: 0.154 AC: 159132 AN: 1030858

Other (OTH) AF: 0.196 AC: 11269 AN: 57394

GnomAD4 genome AF: 0.323 AC: 49084 AN: 151978 Hom.: 12380 Cov.: 32 AF XY: 0.321 AC XY: 23866 AN XY: 74286

African (AFR) AF: 0.709 AC: 29410 AN: 41458

American (AMR) AF: 0.242 AC: 3691 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 625 AN: 3470

East Asian (EAS) AF: 0.124 AC: 639 AN: 5168

South Asian (SAS) AF: 0.209 AC: 1008 AN: 4818

European-Finnish (FIN) AF: 0.201 AC: 2116 AN: 10546

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10846 AN: 67952

Other (OTH) AF: 0.299 AC: 630 AN: 2108

Alfa AF: 0.167 Hom.: 1450

Bravo AF: 0.340

Asia WGS AF: 0.260 AC: 902 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 13, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.30
DANN	Benign	0.63
PhyloP100		0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs217776; hg19: chr5-37350390; COSMIC: COSV51528201; COSMIC: COSV51528201;