NM_153485.3:c.3756C>T

Variant names:

• chr5-37298905-G-A
• rs216400
• NM_153485.3:c.3756C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_153485.3(NUP155):​c.3756C>T​(p.Gly1252Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00529 in 1,612,134 control chromosomes in the GnomAD database, including 413 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.029 (223 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (190 hom.)
• Consequence: NUP155 NM_153485.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.773
• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 5-37298905-G-A is Benign according to our data. Variant chr5-37298905-G-A is described in ClinVar as Benign. ClinVar VariationId is 776039.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.773 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0967 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.3756C>T	p.Gly1252Gly	synonymous	Exon 32 of 35	NP_705618.1	O75694-1
	NUP155	NM_004298.4		c.3579C>T	p.Gly1193Gly	synonymous	Exon 32 of 35	NP_004289.1	O75694-2
	NUP155	NM_001278312.2		c.3564C>T	p.Gly1188Gly	synonymous	Exon 31 of 34	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.3756C>T	p.Gly1252Gly	synonymous	Exon 32 of 35	ENSP00000231498.3	O75694-1
	NUP155	ENST00000381843.6	TSL:1	c.3579C>T	p.Gly1193Gly	synonymous	Exon 32 of 35	ENSP00000371265.2	O75694-2
	NUP155	ENST00000513532.1	TSL:1	c.3564C>T	p.Gly1188Gly	synonymous	Exon 31 of 34	ENSP00000422019.1	E9PF10

Frequencies

GnomAD3 genomes AF: 0.0287 AC: 4369 AN: 152144 Hom.: 223 Cov.: 32

Gnomad AFR AF: 0.0993

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0125

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.0249

GnomAD2 exomes AF: 0.00754 AC: 1895 AN: 251402 AF XY: 0.00526

Gnomad AFR exome AF: 0.104

Gnomad AMR exome AF: 0.00497

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000704

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00285 AC: 4154 AN: 1459872 Hom.: 190 Cov.: 30 AF XY: 0.00237 AC XY: 1721 AN XY: 726422

African (AFR) AF: 0.104 AC: 3453 AN: 33350

American (AMR) AF: 0.00552 AC: 247 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.000255 AC: 22 AN: 86204

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00278 AC: 16 AN: 5760

European-Non Finnish (NFE) AF: 0.0000423 AC: 47 AN: 1110308

Other (OTH) AF: 0.00612 AC: 369 AN: 60328

GnomAD4 genome AF: 0.0287 AC: 4374 AN: 152262 Hom.: 223 Cov.: 32 AF XY: 0.0276 AC XY: 2055 AN XY: 74458

African (AFR) AF: 0.0992 AC: 4120 AN: 41538

American (AMR) AF: 0.0124 AC: 189 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68032

Other (OTH) AF: 0.0246 AC: 52 AN: 2110

Alfa AF: 0.0142 Hom.: 48

Bravo AF: 0.0337

Asia WGS AF: 0.00549 AC: 19 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	8.6
DANN	Benign	0.64
PhyloP100		0.77
Mutation Taster		=95/5	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: rs216400; hg19: chr5-37299007; COSMIC: COSV104371325;