19-49908485-A-G

Position:

chr19-49908485-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016553.5(NUP62):c.1323T>C(p.Asp441Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.932 in 1,614,114 control chromosomes in the GnomAD database, including 701,542 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.95 ( 69048 hom., cov: 33)

Exomes 𝑓: 0.93 ( 632494 hom. )

Consequence

NUP62
NM_016553.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0350

Variant links:

Genes affected

NUP62 (HGNC:8066): (nucleoporin 62) The nuclear pore complex is a massive structure that extends across the nuclear envelope, forming a gateway that regulates the flow of macromolecules between the nucleus and the cytoplasm. Nucleoporins are the main components of the nuclear pore complex in eukaryotic cells. The protein encoded by this gene is a member of the FG-repeat containing nucleoporins and is localized to the nuclear pore central plug. This protein associates with the importin alpha/beta complex which is involved in the import of proteins containing nuclear localization signals. Multiple transcript variants of this gene encode a single protein isoform. [provided by RefSeq, Jul 2008]

NUP62 links:

IL4I1 (HGNC:19094): (interleukin 4 induced 1) This gene encodes a secreted L-amino acid oxidase protein which primarily catabolizes L-phenylalanine and, to a lesser extent, L-arginine. The expression of this gene is induced by the cytokine interleukin 4 in B cells. This gene is also expressed in macrophages and dendritic cells. This protein may play a role immune system escape as it is expressed in tumor-associated macrophages and suppresses T-cell responses. This protein also contains domains thought to be involved in the binding of flavin adenine dinucleotide (FAD) cofactor. Multiple transcript variants encoding different isoforms have been found for this gene. Some transcripts of this gene share a promoter and exons of the 5' UTR with the overlapping NUP62 gene. [provided by RefSeq, Jul 2020]

IL4I1 links:

IL4I1 (HGNC:):

IL4I1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 19-49908485-A-G is Benign according to our data. Variant chr19-49908485-A-G is described in ClinVar as [Benign]. Clinvar id is 129846.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-49908485-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.979 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUP62	NM_016553.5 linkuse as main transcript	c.1323T>C	p.Asp441Asp	synonymous_variant	3/3	ENST00000352066.8	NP_057637.2	P37198A0A024QZF1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUP62	ENST00000352066.8 linkuse as main transcript	c.1323T>C	p.Asp441Asp	synonymous_variant	3/3	1	NM_016553.5	ENSP00000305503.3		P37198

Frequencies

GnomAD3 genomes

AF:

0.952

AC:

144864

AN:

152202

Hom.:

68987

Cov.:

show subpopulations

Gnomad AFR

AF:

0.987

Gnomad AMI

AF:

0.935

Gnomad AMR

AF:

0.956

Gnomad ASJ

AF:

0.905

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.945

Gnomad FIN

AF:

0.941

Gnomad MID

AF:

0.956

Gnomad NFE

AF:

0.930

Gnomad OTH

AF:

0.943

GnomAD3 exomes

AF:

0.944

AC:

236360

AN:

250348

Hom.:

111671

AF XY:

0.942

AC XY:

127432

AN XY:

135282

show subpopulations

Gnomad AFR exome

AF:

0.990

Gnomad AMR exome

AF:

0.967

Gnomad ASJ exome

AF:

0.900

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.946

Gnomad FIN exome

AF:

0.940

Gnomad NFE exome

AF:

0.926

Gnomad OTH exome

AF:

0.932

GnomAD4 exome

AF:

0.930

AC:

1359454

AN:

1461794

Hom.:

632494

Cov.:

100

AF XY:

0.930

AC XY:

676292

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.989

Gnomad4 AMR exome

AF:

0.967

Gnomad4 ASJ exome

AF:

0.899

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.945

Gnomad4 FIN exome

AF:

0.940

Gnomad4 NFE exome

AF:

0.923

Gnomad4 OTH exome

AF:

0.935

GnomAD4 genome

AF:

0.952

AC:

144984

AN:

152320

Hom.:

69048

Cov.:

AF XY:

0.953

AC XY:

70955

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.987

Gnomad4 AMR

AF:

0.957

Gnomad4 ASJ

AF:

0.905

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.945

Gnomad4 FIN

AF:

0.941

Gnomad4 NFE

AF:

0.930

Gnomad4 OTH

AF:

0.944

Alfa

AF:

0.934

Hom.:

36682

Bravo

AF:

0.954

Asia WGS

AF:

0.973

AC:

3383

AN:

3478

EpiCase

AF:

0.929

EpiControl

AF:

0.927

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 31, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 98% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy, Progressive Myoclonus Epilepsy and Abnormal Movements and Neurodegeneration with brain iron accumulation. Number of patients: 91. Only high quality variants are reported. -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Infantile bilateral striatal necrosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.087

DANN

Benign

0.58

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over