rs217816

Variant names:

• chr5-37294294-G-A
• rs217816
• NM_153485.3:c.3930+35C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-37294294-G-A
• chr5-37294294-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_153485.3(NUP155):​c.3930+35C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000801 in 1,248,450 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: NUP155 NM_153485.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

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.3930+35C>T		intron	N/A	NP_705618.1	O75694-1
	NUP155	NM_004298.4		c.3753+35C>T		intron	N/A	NP_004289.1	O75694-2
	NUP155	NM_001278312.2		c.3738+35C>T		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.3930+35C>T		intron	N/A	ENSP00000231498.3	O75694-1
	NUP155	ENST00000381843.6	TSL:1	c.3753+35C>T		intron	N/A	ENSP00000371265.2	O75694-2
	NUP155	ENST00000513532.1	TSL:1	c.3738+35C>T		intron	N/A	ENSP00000422019.1	E9PF10

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 8.01e-7 AC: 1 AN: 1248450 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 622774

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 28540

American (AMR) AF: 0.00 AC: 0 AN: 34696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24002

East Asian (EAS) AF: 0.00 AC: 0 AN: 34612

South Asian (SAS) AF: 0.00 AC: 0 AN: 73848

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48302

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4262

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 947508

Other (OTH) AF: 0.0000190 AC: 1 AN: 52680

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.021
DANN	Benign	0.61
PhyloP100		-1.7

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: rs217816; hg19: chr5-37294396;