NM_153485.3:c.4038-227G>C

Variant names:

• chr5-37292265-C-G
• rs216393
• NM_153485.3:c.4038-227G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_153485.3(NUP155):​c.4038-227G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 151,006 control chromosomes in the GnomAD database, including 22,365 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.51 (22365 hom., cov: 28)
• Consequence: NUP155 NM_153485.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.82
• Publications: 2 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BP6: Variant 5-37292265-C-G is Benign according to our data. Variant chr5-37292265-C-G is described in ClinVar as Benign. ClinVar VariationId is 1263135.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

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.4038-227G>C		intron	N/A	NP_705618.1	O75694-1
	NUP155	NM_004298.4		c.3861-227G>C		intron	N/A	NP_004289.1	O75694-2
	NUP155	NM_001278312.2		c.3846-227G>C		intron	N/A	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.4038-227G>C		intron	N/A	ENSP00000231498.3	O75694-1
	NUP155	ENST00000381843.6	TSL:1	c.3861-227G>C		intron	N/A	ENSP00000371265.2	O75694-2
	NUP155	ENST00000513532.1	TSL:1	c.3846-227G>C		intron	N/A	ENSP00000422019.1	E9PF10

Frequencies

GnomAD3 genomes AF: 0.509 AC: 76772 AN: 150894 Hom.: 22303 Cov.: 28

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.505

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.509 AC: 76890 AN: 151006 Hom.: 22365 Cov.: 28 AF XY: 0.509 AC XY: 37530 AN XY: 73696

African (AFR) AF: 0.815 AC: 33602 AN: 41228

American (AMR) AF: 0.444 AC: 6726 AN: 15156

Ashkenazi Jewish (ASJ) AF: 0.430 AC: 1486 AN: 3458

East Asian (EAS) AF: 0.400 AC: 2042 AN: 5108

South Asian (SAS) AF: 0.439 AC: 2088 AN: 4760

European-Finnish (FIN) AF: 0.395 AC: 4073 AN: 10300

Middle Eastern (MID) AF: 0.500 AC: 145 AN: 290

European-Non Finnish (NFE) AF: 0.374 AC: 25330 AN: 67698

Other (OTH) AF: 0.512 AC: 1075 AN: 2098

Alfa AF: 0.261 Hom.: 580

Bravo AF: 0.526

Asia WGS AF: 0.466 AC: 1619 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.51
DANN	Benign	0.76
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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: rs216393; hg19: chr5-37292367;