chr5-37294371-T-C

Variant names:

• chr5-37294371-T-C
• rs1045908
• NM_153485.3:c.3888A>G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_153485.3(NUP155):​c.3888A>G​(p.Leu1296Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 1,597,574 control chromosomes in the GnomAD database, including 68,437 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5186 hom., cov: 31)
  • Exomes 𝑓: 0.29 (63251 hom.)
• Consequence: NUP155 NM_153485.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.05

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 5-37294371-T-C is Benign according to our data. Variant chr5-37294371-T-C is described in ClinVar as [Benign]. Clinvar id is 1294896.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.05 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUP155	NM_153485.3	c.3888A>G	p.Leu1296Leu	synonymous_variant	Exon 33 of 35	ENST00000231498.8	NP_705618.1
NUP155	NM_004298.4	c.3711A>G	p.Leu1237Leu	synonymous_variant	Exon 33 of 35		NP_004289.1
NUP155	NM_001278312.2	c.3696A>G	p.Leu1232Leu	synonymous_variant	Exon 32 of 34		NP_001265241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUP155	ENST00000231498.8	c.3888A>G	p.Leu1296Leu	synonymous_variant	Exon 33 of 35	1	NM_153485.3	ENSP00000231498.3
NUP155	ENST00000381843.6	c.3711A>G	p.Leu1237Leu	synonymous_variant	Exon 33 of 35	1		ENSP00000371265.2
NUP155	ENST00000513532.1	c.3696A>G	p.Leu1232Leu	synonymous_variant	Exon 32 of 34	1		ENSP00000422019.1
NUP155	ENST00000502533.5	n.1546A>G		non_coding_transcript_exon_variant	Exon 12 of 14	5

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37935 AN: 151924 Hom.: 5182 Cov.: 31

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.269

GnomAD3 exomes AF: 0.294 AC: 73434 AN: 249696 Hom.: 11254 AF XY: 0.301 AC XY: 40574 AN XY: 134980

Gnomad AFR exome AF: 0.132

Gnomad AMR exome AF: 0.291

Gnomad ASJ exome AF: 0.354

Gnomad EAS exome AF: 0.388

Gnomad SAS exome AF: 0.370

Gnomad FIN exome AF: 0.224

Gnomad NFE exome AF: 0.289

Gnomad OTH exome AF: 0.313

GnomAD4 exome AF: 0.292 AC: 421869 AN: 1445534 Hom.: 63251 Cov.: 29 AF XY: 0.295 AC XY: 212435 AN XY: 720062

Gnomad4 AFR exome AF: 0.124

Gnomad4 AMR exome AF: 0.290

Gnomad4 ASJ exome AF: 0.347

Gnomad4 EAS exome AF: 0.382

Gnomad4 SAS exome AF: 0.364

Gnomad4 FIN exome AF: 0.225

Gnomad4 NFE exome AF: 0.289

Gnomad4 OTH exome AF: 0.303

GnomAD4 genome AF: 0.250 AC: 37949 AN: 152040 Hom.: 5186 Cov.: 31 AF XY: 0.250 AC XY: 18593 AN XY: 74318

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.362

Gnomad4 EAS AF: 0.375

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.268

Alfa AF: 0.286 Hom.: 10661

Bravo AF: 0.250

Asia WGS AF: 0.306 AC: 1065 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

NUP155-related disorder Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	8.0
DANN	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs1045908; hg19: chr5-37294473; COSMIC: COSV51528228; COSMIC: COSV51528228;