chr5-37291881-T-C

Variant names:

• chr5-37291881-T-C
• rs216391
• NM_153485.3:c.*19A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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 -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 VariationId 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.

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.*19A>G		3_prime_UTR	Exon 35 of 35	NP_705618.1	O75694-1
	NUP155	NM_004298.4		c.*19A>G		3_prime_UTR	Exon 35 of 35	NP_004289.1	O75694-2
	NUP155	NM_001278312.2		c.*19A>G		3_prime_UTR	Exon 34 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.*19A>G		3_prime_UTR	Exon 35 of 35	ENSP00000231498.3	O75694-1
	NUP155	ENST00000381843.6	TSL:1	c.*19A>G		3_prime_UTR	Exon 35 of 35	ENSP00000371265.2	O75694-2
	NUP155	ENST00000969938.1		c.*19A>G		3_prime_UTR	Exon 36 of 36	ENSP00000639997.1

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

GnomAD2 exomes AF: 0.00750 AC: 1885 AN: 251250 AF XY: 0.00526

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 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

African (AFR) AF: 0.104 AC: 3473 AN: 33394

American (AMR) AF: 0.00552 AC: 247 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39656

South Asian (SAS) AF: 0.000255 AC: 22 AN: 86194

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.00278 AC: 16 AN: 5756

European-Non Finnish (NFE) AF: 0.0000432 AC: 48 AN: 1109936

Other (OTH) AF: 0.00612 AC: 369 AN: 60316

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

African (AFR) AF: 0.0990 AC: 4110 AN: 41536

American (AMR) AF: 0.0124 AC: 189 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

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

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68020

Other (OTH) AF: 0.0246 AC: 52 AN: 2114

Alfa AF: 0.0141 Hom.: 42

Bravo AF: 0.0337

Asia WGS AF: 0.00549 AC: 19 AN: 3476

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	-0.84
CADD	Benign	1.9
DANN	Benign	0.41
PhyloP100		-0.23
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs216391; hg19: chr5-37291983;