chr5-37298779-T-C

Position:

• chr5-37298779-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.3793+89A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00792 in 769,208 control chromosomes in the GnomAD database, including 296 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (202 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (94 hom.)
• Consequence: NUP155 NM_153485.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.553

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 5-37298779-T-C is Benign according to our data. Variant chr5-37298779-T-C is described in ClinVar as [Benign]. Clinvar id is 1263247.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0906 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUP155	NM_153485.3	c.3793+89A>G		intron_variant		ENST00000231498.8
NUP155	NM_001278312.2	c.3601+89A>G		intron_variant
NUP155	NM_004298.4	c.3616+89A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP155	ENST00000231498.8	c.3793+89A>G		intron_variant		1	NM_153485.3	P1
NUP155	ENST00000381843.6	c.3616+89A>G		intron_variant		1
NUP155	ENST00000513532.1	c.3601+89A>G		intron_variant		1
NUP155	ENST00000502533.5	n.1451+89A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0270 AC: 4102 AN: 152182 Hom.: 202 Cov.: 32

Gnomad AFR AF: 0.0932

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0120

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.0220

GnomAD4 exome AF: 0.00321 AC: 1982 AN: 616908 Hom.: 94 AF XY: 0.00242 AC XY: 803 AN XY: 331700

Gnomad4 AFR exome AF: 0.0920

Gnomad4 AMR exome AF: 0.00506

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000235

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000770

Gnomad4 OTH exome AF: 0.00701

GnomAD4 genome AF: 0.0270 AC: 4108 AN: 152300 Hom.: 202 Cov.: 32 AF XY: 0.0260 AC XY: 1936 AN XY: 74486

Gnomad4 AFR AF: 0.0931

Gnomad4 AMR AF: 0.0119

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: 0.0218

Alfa AF: 0.0325 Hom.: 34

Bravo AF: 0.0317

Asia WGS AF: 0.00520 AC: 18 AN: 3478

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	-0.86
CADD	Benign	4.9
DANN	Benign	0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs216399; hg19: chr5-37298881; COSMIC: COSV104371324; COSMIC: COSV104371324;