Variant 1-154025700-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000368559.8(NUP210L):c.3964G>A(p.Val1322Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00105 in 1,612,574 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00098 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0011 ( 3 hom. )

Consequence

NUP210L
ENST00000368559.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.70

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0142939985).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUP210L	NM_207308.3 linkuse as main transcript	c.3964G>A	p.Val1322Met	missense_variant	30/40	ENST00000368559.8	NP_997191.2
NUP210L	XM_011510122.2 linkuse as main transcript	c.3832G>A	p.Val1278Met	missense_variant	29/39		XP_011508424.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUP210L	ENST00000368559.8 linkuse as main transcript	c.3964G>A	p.Val1322Met	missense_variant	30/40	5	NM_207308.3	ENSP00000357547	P2	Q5VU65-1
NUP210L	ENST00000368553.5 linkuse as main transcript	c.763G>A	p.Val255Met	missense_variant	8/16	1		ENSP00000357541	A2
NUP210L	ENST00000271854.3 linkuse as main transcript	c.3964G>A	p.Val1322Met	missense_variant	30/38	5		ENSP00000271854	A2	Q5VU65-2

Frequencies

GnomAD3 genomes

AF:

0.000980

AC:

149

AN:

151990

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000387

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00269

Gnomad ASJ

AF:

0.00864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000947

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000809

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000967

AC:

241

AN:

249240

Hom.:

AF XY:

0.000887

AC XY:

120

AN XY:

135240

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.00154

Gnomad ASJ exome

AF:

0.00736

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000919

Gnomad OTH exome

AF:

0.00132

GnomAD4 exome

AF:

0.00106

AC:

1543

AN:

1460466

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

743

AN XY:

726528

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.00152

Gnomad4 ASJ exome

AF:

0.00839

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00105

Gnomad4 OTH exome

AF:

0.00136

GnomAD4 genome

AF:

0.000980

AC:

149

AN:

152108

Hom.:

Cov.:

AF XY:

0.00116

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.000386

Gnomad4 AMR

AF:

0.00269

Gnomad4 ASJ

AF:

0.00864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000947

Gnomad4 NFE

AF:

0.000809

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00119

Hom.:

Bravo

AF:

0.00112

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00133

AC:

ExAC

AF:

0.000745

AC:

EpiCase

AF:

0.00121

EpiControl

AF:

0.000771

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

Aug 09, 2021

The c.3964G>A (p.V1322M) alteration is located in exon 30 (coding exon 30) of the NUP210L gene. This alteration results from a G to A substitution at nucleotide position 3964, causing the valine (V) at amino acid position 1322 to be replaced by a methionine (M). 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

0.23

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;T;.

Eigen

Benign

0.13

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.86

D;T;D

M_CAP

Benign

0.0077

MetaRNN

Benign

0.014

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;.;L

MutationTaster

Benign

0.63

D;D;D

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.58

N;N;N

REVEL

Benign

0.15

Sift

Benign

0.19

T;T;T

Sift4G

Uncertain

0.012

D;D;D

Polyphen

0.94

P;.;.

Vest4

0.59

MVP

0.49

MPC

0.77

ClinPred

0.030

GERP RS

4.9

Varity_R

0.046

gMVP

0.33

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