rs216377

Positions:

• chr5-37336609-A-G
• chr5-37336609-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153485.3(NUP155):​c.1347+1209T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 151,796 control chromosomes in the GnomAD database, including 12,353 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.32 (12353 hom., cov: 31)
• Consequence: NUP155 NM_153485.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUP155	NM_153485.3	c.1347+1209T>C		intron_variant		ENST00000231498.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP155	ENST00000231498.8	c.1347+1209T>C		intron_variant		1	NM_153485.3	P1
NUP155	ENST00000381843.6	c.1170+1209T>C		intron_variant		1
NUP155	ENST00000513532.1	c.1347+1209T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48915 AN: 151678 Hom.: 12316 Cov.: 31

Gnomad AFR AF: 0.709

Gnomad AMI AF: 0.0727

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.292

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.323 AC: 49014 AN: 151796 Hom.: 12353 Cov.: 31 AF XY: 0.321 AC XY: 23831 AN XY: 74162

Gnomad4 AFR AF: 0.709

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.299

Alfa AF: 0.238 Hom.: 847

Bravo AF: 0.340

Asia WGS AF: 0.260 AC: 903 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.6
DANN	Benign	0.28

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: rs216377; hg19: chr5-37336711; COSMIC: COSV51533542;