1-153992935-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4

The ENST00000368559.8(NUP210L):c.5567G>A(p.Gly1856Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000106 in 1,610,526 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

NUP210L
ENST00000368559.8 missense, splice_region

Scores

Splicing: ADA: 0.8677

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.25

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 Uncertain_significance. Variant got 2 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=0.39885858).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUP210L	NM_207308.3 linkuse as main transcript	c.5567G>A	p.Gly1856Asp	missense_variant, splice_region_variant	40/40	ENST00000368559.8
NUP210L	XM_011510122.2 linkuse as main transcript	c.5435G>A	p.Gly1812Asp	missense_variant, splice_region_variant	39/39

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP210L	ENST00000368559.8 linkuse as main transcript	c.5567G>A	p.Gly1856Asp	missense_variant, splice_region_variant	40/40	5	NM_207308.3	P2	Q5VU65-1
NUP210L	ENST00000368553.5 linkuse as main transcript	c.1910G>A	p.Gly637Asp	missense_variant, splice_region_variant	16/16	1		A2
NUP210L	ENST00000271854.3 linkuse as main transcript	c.5111G>A	p.Gly1704Asp	missense_variant, splice_region_variant	38/38	5		A2	Q5VU65-2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

151960

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000122

AC:

AN:

246432

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

133798

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000666

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000890

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000960

AC:

AN:

1458448

Hom.:

Cov.:

AF XY:

0.0000152

AC XY:

AN XY:

725578

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152078

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000312

Hom.:

ExAC

AF:

0.0000166

AC:

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

Mar 29, 2022

The c.5567G>A (p.G1856D) alteration is located in exon 40 (coding exon 40) of the NUP210L gene. This alteration results from a G to A substitution at nucleotide position 5567, causing the glycine (G) at amino acid position 1856 to be replaced by an aspartic acid (D). 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

0.096

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.22

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.096

T;T;.

Eigen

Benign

0.12

Eigen_PC

Benign

0.035

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.54

T;T;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.40

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;.;.

MutationTaster

Benign

0.85

D;N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.9

N;N;N

REVEL

Benign

0.11

Sift

Benign

0.20

T;D;D

Sift4G

Uncertain

0.042

D;D;D

Polyphen

0.99

D;.;.

Vest4

0.60

MutPred

0.23

Gain of solvent accessibility (P = 0.0354);.;.;

MVP

0.78

MPC

0.38

ClinPred

0.31

GERP RS

4.1

Varity_R

0.11

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.87

dbscSNV1_RF

Benign

0.59

SpliceAI score (max)

0.020

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