5-37293113-A-G

Variant names:

• chr5-37293113-A-G
• rs2272602
• NM_153485.3:c.3931-128T>C

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.3931-128T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 669,844 control chromosomes in the GnomAD database, including 9,228 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (1981 hom., cov: 32)
  • Exomes 𝑓: 0.16 (7247 hom.)
• Consequence: NUP155 NM_153485.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.838
• 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: 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=-0.91).
• BP6: Variant 5-37293113-A-G is Benign according to our data. Variant chr5-37293113-A-G is described in ClinVar as Benign. ClinVar VariationId is 1251251.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.189 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.3931-128T>C		intron	N/A	NP_705618.1	O75694-1
	NUP155	NM_004298.4		c.3754-128T>C		intron	N/A	NP_004289.1	O75694-2
	NUP155	NM_001278312.2		c.3739-128T>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.3931-128T>C		intron	N/A	ENSP00000231498.3	O75694-1
	NUP155	ENST00000381843.6	TSL:1	c.3754-128T>C		intron	N/A	ENSP00000371265.2	O75694-2
	NUP155	ENST00000513532.1	TSL:1	c.3739-128T>C		intron	N/A	ENSP00000422019.1	E9PF10

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24236 AN: 152084 Hom.: 1971 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.169

GnomAD4 exome AF: 0.163 AC: 84189 AN: 517642 Hom.: 7247 Cov.: 5 AF XY: 0.165 AC XY: 46283 AN XY: 280374

African (AFR) AF: 0.147 AC: 1994 AN: 13568

American (AMR) AF: 0.189 AC: 4354 AN: 23030

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 3030 AN: 16582

East Asian (EAS) AF: 0.0970 AC: 3120 AN: 32154

South Asian (SAS) AF: 0.199 AC: 10787 AN: 54306

European-Finnish (FIN) AF: 0.203 AC: 9256 AN: 45576

Middle Eastern (MID) AF: 0.167 AC: 363 AN: 2172

European-Non Finnish (NFE) AF: 0.155 AC: 46954 AN: 302144

Other (OTH) AF: 0.154 AC: 4331 AN: 28110

GnomAD4 genome AF: 0.160 AC: 24277 AN: 152202 Hom.: 1981 Cov.: 32 AF XY: 0.163 AC XY: 12159 AN XY: 74404

African (AFR) AF: 0.149 AC: 6175 AN: 41540

American (AMR) AF: 0.180 AC: 2753 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 621 AN: 3472

East Asian (EAS) AF: 0.125 AC: 647 AN: 5192

South Asian (SAS) AF: 0.200 AC: 963 AN: 4826

European-Finnish (FIN) AF: 0.200 AC: 2115 AN: 10584

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10529 AN: 67998

Other (OTH) AF: 0.178 AC: 375 AN: 2110

Alfa AF: 0.156 Hom.: 238

Bravo AF: 0.155

Asia WGS AF: 0.228 AC: 788 AN: 3470

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.20
DANN	Benign	0.70
PhyloP100		-0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs2272602; hg19: chr5-37293215;