5-37291881-T-C

Position:

• chr5-37291881-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_153485.3(NUP155):​c.*19A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0053 in 1,611,708 control chromosomes in the GnomAD database, including 415 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.029 (222 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (193 hom.)
• Consequence: NUP155 NM_153485.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.226

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 5-37291881-T-C is Benign according to our data. Variant chr5-37291881-T-C is described in ClinVar as [Benign]. Clinvar id is 1270364.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUP155	NM_153485.3	c.*19A>G		3_prime_UTR_variant	35/35	ENST00000231498.8	NP_705618.1
NUP155	NM_004298.4	c.*19A>G		3_prime_UTR_variant	35/35		NP_004289.1
NUP155	NM_001278312.2	c.*19A>G		3_prime_UTR_variant	34/34		NP_001265241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUP155	ENST00000231498	c.*19A>G		3_prime_UTR_variant	35/35	1	NM_153485.3	ENSP00000231498.3

Frequencies

GnomAD3 genomes AF: 0.0287 AC: 4359 AN: 152132 Hom.: 222 Cov.: 32

Gnomad AFR AF: 0.0991

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.0249

GnomAD3 exomes AF: 0.00750 AC: 1885 AN: 251250 Hom.: 102 AF XY: 0.00526 AC XY: 715 AN XY: 135850

Gnomad AFR exome AF: 0.104

Gnomad AMR exome AF: 0.00495

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000261

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000704

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00286 AC: 4175 AN: 1459458 Hom.: 193 Cov.: 29 AF XY: 0.00239 AC XY: 1733 AN XY: 726228

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.00552

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000255

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000432

Gnomad4 OTH exome AF: 0.00612

GnomAD4 genome AF: 0.0287 AC: 4364 AN: 152250 Hom.: 222 Cov.: 32 AF XY: 0.0275 AC XY: 2050 AN XY: 74444

Gnomad4 AFR AF: 0.0990

Gnomad4 AMR AF: 0.0124

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.0246

Alfa AF: 0.0124 Hom.: 34

Bravo AF: 0.0337

Asia WGS AF: 0.00549 AC: 19 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 13, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs216391; hg19: chr5-37291983;