rs216377

Variant names:

• chr5-37336609-A-G
• rs216377
• NM_153485.3:c.1347+1209T>C

Your query was ambiguous. Multiple possible variants found:

• chr5-37336609-A-G
• chr5-37336609-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153485.3(NUP155):​c.1347+1209T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 151,796 control chromosomes in the GnomAD database, including 12,353 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.32 (12353 hom., cov: 31)
• Consequence: NUP155 NM_153485.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUP155	NM_153485.3	c.1347+1209T>C		intron_variant	Intron 12 of 34	ENST00000231498.8	NP_705618.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUP155	ENST00000231498.8	c.1347+1209T>C		intron_variant	Intron 12 of 34	1	NM_153485.3	ENSP00000231498.3
NUP155	ENST00000381843.6	c.1170+1209T>C		intron_variant	Intron 12 of 34	1		ENSP00000371265.2
NUP155	ENST00000513532.1	c.1347+1209T>C		intron_variant	Intron 12 of 33	1		ENSP00000422019.1
NUP155	ENST00000716591.1	c.1347+1209T>C		intron_variant	Intron 12 of 34			ENSP00000520564.1

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48915 AN: 151678 Hom.: 12316 Cov.: 31

Gnomad AFR AF: 0.709

Gnomad AMI AF: 0.0727

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.323 AC: 49014 AN: 151796 Hom.: 12353 Cov.: 31 AF XY: 0.321 AC XY: 23831 AN XY: 74162

African (AFR) AF: 0.709 AC: 29353 AN: 41396

American (AMR) AF: 0.242 AC: 3675 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 627 AN: 3464

East Asian (EAS) AF: 0.124 AC: 643 AN: 5172

South Asian (SAS) AF: 0.210 AC: 1009 AN: 4802

European-Finnish (FIN) AF: 0.201 AC: 2109 AN: 10518

Middle Eastern (MID) AF: 0.182 AC: 53 AN: 292

European-Non Finnish (NFE) AF: 0.160 AC: 10847 AN: 67924

Other (OTH) AF: 0.299 AC: 632 AN: 2114

Alfa AF: 0.238 Hom.: 847

Bravo AF: 0.340

Asia WGS AF: 0.260 AC: 903 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.6
DANN	Benign	0.28
PhyloP100		0.026
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: rs216377; hg19: chr5-37336711; COSMIC: COSV51533542;