chr5-37298779-T-C

Variant names:

• chr5-37298779-T-C
• rs216399
• NM_153485.3:c.3793+89A>G

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.3793+89A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00792 in 769,208 control chromosomes in the GnomAD database, including 296 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (202 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (94 hom.)
• Consequence: NUP155 NM_153485.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.553
• 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=-0.86).
• BP6: Variant 5-37298779-T-C is Benign according to our data. Variant chr5-37298779-T-C is described in ClinVar as Benign. ClinVar VariationId is 1263247.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0906 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.3793+89A>G		intron	N/A	NP_705618.1	O75694-1
	NUP155	NM_004298.4		c.3616+89A>G		intron	N/A	NP_004289.1	O75694-2
	NUP155	NM_001278312.2		c.3601+89A>G		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.3793+89A>G		intron	N/A	ENSP00000231498.3	O75694-1
	NUP155	ENST00000381843.6	TSL:1	c.3616+89A>G		intron	N/A	ENSP00000371265.2	O75694-2
	NUP155	ENST00000513532.1	TSL:1	c.3601+89A>G		intron	N/A	ENSP00000422019.1	E9PF10

Frequencies

GnomAD3 genomes AF: 0.0270 AC: 4102 AN: 152182 Hom.: 202 Cov.: 32

Gnomad AFR AF: 0.0932

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0120

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.0220

GnomAD4 exome AF: 0.00321 AC: 1982 AN: 616908 Hom.: 94 AF XY: 0.00242 AC XY: 803 AN XY: 331700

African (AFR) AF: 0.0920 AC: 1520 AN: 16516

American (AMR) AF: 0.00506 AC: 180 AN: 35574

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20316

East Asian (EAS) AF: 0.00 AC: 0 AN: 33002

South Asian (SAS) AF: 0.000235 AC: 15 AN: 63908

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47234

Middle Eastern (MID) AF: 0.00287 AC: 12 AN: 4178

European-Non Finnish (NFE) AF: 0.0000770 AC: 28 AN: 363784

Other (OTH) AF: 0.00701 AC: 227 AN: 32396

GnomAD4 genome AF: 0.0270 AC: 4108 AN: 152300 Hom.: 202 Cov.: 32 AF XY: 0.0260 AC XY: 1936 AN XY: 74486

African (AFR) AF: 0.0931 AC: 3867 AN: 41548

American (AMR) AF: 0.0119 AC: 182 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68026

Other (OTH) AF: 0.0218 AC: 46 AN: 2114

Alfa AF: 0.0337 Hom.: 34

Bravo AF: 0.0317

Asia WGS AF: 0.00520 AC: 18 AN: 3478

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	-0.86
CADD	Benign	4.9
DANN	Benign	0.32
PhyloP100		0.55
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)		0.0		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: rs216399; hg19: chr5-37298881; COSMIC: COSV104371324;