NM_153485.3:c.3714G>A

Variant names:

• chr5-37298947-C-T
• rs16903575
• NM_153485.3:c.3714G>A

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.3714G>A​(p.Ser1238Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00511 in 1,612,238 control chromosomes in the GnomAD database, including 336 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (171 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (165 hom.)
• Consequence: NUP155 NM_153485.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0510
• 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=-0.41).
• BP6: Variant 5-37298947-C-T is Benign according to our data. Variant chr5-37298947-C-T is described in ClinVar as Benign. ClinVar VariationId is 767997.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.051 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0909 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.3714G>A	p.Ser1238Ser	synonymous	Exon 32 of 35	NP_705618.1	O75694-1
	NUP155	NM_004298.4		c.3537G>A	p.Ser1179Ser	synonymous	Exon 32 of 35	NP_004289.1	O75694-2
	NUP155	NM_001278312.2		c.3522G>A	p.Ser1174Ser	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.3714G>A	p.Ser1238Ser	synonymous	Exon 32 of 35	ENSP00000231498.3	O75694-1
	NUP155	ENST00000381843.6	TSL:1	c.3537G>A	p.Ser1179Ser	synonymous	Exon 32 of 35	ENSP00000371265.2	O75694-2
	NUP155	ENST00000513532.1	TSL:1	c.3522G>A	p.Ser1174Ser	synonymous	Exon 31 of 34	ENSP00000422019.1	E9PF10

Frequencies

GnomAD3 genomes AF: 0.0267 AC: 4063 AN: 152086 Hom.: 168 Cov.: 32

Gnomad AFR AF: 0.0929

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00976

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.0201

GnomAD2 exomes AF: 0.00703 AC: 1767 AN: 251322 AF XY: 0.00510

Gnomad AFR exome AF: 0.0957

Gnomad AMR exome AF: 0.00448

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000273

Gnomad OTH exome AF: 0.00294

GnomAD4 exome AF: 0.00284 AC: 4146 AN: 1460034 Hom.: 165 Cov.: 30 AF XY: 0.00242 AC XY: 1755 AN XY: 726504

African (AFR) AF: 0.0982 AC: 3278 AN: 33378

American (AMR) AF: 0.00485 AC: 217 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39666

South Asian (SAS) AF: 0.000302 AC: 26 AN: 86220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00399 AC: 23 AN: 5764

European-Non Finnish (NFE) AF: 0.000203 AC: 225 AN: 1110430

Other (OTH) AF: 0.00623 AC: 376 AN: 60330

GnomAD4 genome AF: 0.0269 AC: 4091 AN: 152204 Hom.: 171 Cov.: 32 AF XY: 0.0264 AC XY: 1963 AN XY: 74420

African (AFR) AF: 0.0934 AC: 3876 AN: 41518

American (AMR) AF: 0.00974 AC: 149 AN: 15294

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.0137 AC: 4 AN: 292

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68008

Other (OTH) AF: 0.0199 AC: 42 AN: 2112

Alfa AF: 0.0126 Hom.: 54

Bravo AF: 0.0305

Asia WGS AF: 0.00606 AC: 23 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000296

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	-0.41
CADD	Benign	11
DANN	Benign	0.50
PhyloP100		-0.051
Mutation Taster		=97/3	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: rs16903575; hg19: chr5-37299049; COSMIC: COSV51536756; COSMIC: COSV51536756;