Variant 1-154001018-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_Strong

The ENST00000368559.8(NUP210L):c.5224C>A(p.His1742Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000159 in 1,614,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H1742R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

NUP210L
ENST00000368559.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.753

Variant links:

Genes affected

NUP210L (HGNC:29915): (nucleoporin 210 like) Predicted to act upstream of or within Sertoli cell development and spermatid development. Predicted to be integral component of membrane. Predicted to be part of nuclear pore. [provided by Alliance of Genome Resources, Apr 2022]

NUP210L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant where missense usually causes diseases, NUP210L

BP4

Computational evidence support a benign effect (MetaRNN=0.061033726).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUP210L	NM_207308.3 linkuse as main transcript	c.5224C>A	p.His1742Asn	missense_variant	37/40	ENST00000368559.8
NUP210L	XM_011510122.2 linkuse as main transcript	c.5092C>A	p.His1698Asn	missense_variant	36/39

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP210L	ENST00000368559.8 linkuse as main transcript	c.5224C>A	p.His1742Asn	missense_variant	37/40	5	NM_207308.3	P2	Q5VU65-1
NUP210L	ENST00000368553.5 linkuse as main transcript	c.1730-5838C>A		intron_variant		1		A2
NUP210L	ENST00000271854.3 linkuse as main transcript	c.4931-5838C>A		intron_variant		5		A2	Q5VU65-2

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000120

AC:

AN:

249520

Hom.:

AF XY:

0.000126

AC XY:

AN XY:

135366

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.000261

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000168

AC:

245

AN:

1461864

Hom.:

Cov.:

AF XY:

0.000179

AC XY:

130

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000206

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000110

Hom.:

Bravo

AF:

0.000110

ESP6500AA

AF:

0.000266

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000993

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 06, 2022

The c.5224C>A (p.H1742N) alteration is located in exon 37 (coding exon 37) of the NUP210L gene. This alteration results from a C to A substitution at nucleotide position 5224, causing the histidine (H) at amino acid position 1742 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.76

Cadd

Benign

8.5

Dann

Benign

0.80

DEOGEN2

Benign

0.067

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.52

M_CAP

Benign

0.0044

MetaRNN

Benign

0.061

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.7

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.21

PROVEAN

Benign

-1.2

REVEL

Benign

0.055

Sift

Benign

0.15

Sift4G

Benign

0.52

Polyphen

0.011

Vest4

0.22

MVP

0.52

MPC

0.35

ClinPred

0.029

GERP RS

3.6

Varity_R

0.058

gMVP

0.28

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

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