Variant chr11-2958434-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_005969.4(NAP1L4):c.857A>T(p.Asn286Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000252 in 1,614,108 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00027 ( 1 hom. )

Consequence

NAP1L4
NM_005969.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.86

Variant links:

Genes affected

NAP1L4 (HGNC:7640): (nucleosome assembly protein 1 like 4) This gene encodes a member of the nucleosome assembly protein (NAP) family which can interact with both core and linker histones. It can shuttle between the cytoplasm and nucleus, suggesting a role as a histone chaperone. This gene is one of several located near the imprinted gene domain of 11p15.5, an important tumor-suppressor gene region. Alterations in this region have been associated with the Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian, and breast cancer. [provided by RefSeq, Jul 2008]

NAP1L4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 15 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAP1L4	NM_005969.4 linkuse as main transcript	c.857A>T	p.Asn286Ile	missense_variant	10/16	ENST00000380542.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAP1L4	ENST00000380542.9 linkuse as main transcript	c.857A>T	p.Asn286Ile	missense_variant	10/16	1	NM_005969.4		Q99733-1

Frequencies

GnomAD3 genomes

AF:

0.0000985

AC:

AN:

152262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000206

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000108

AC:

AN:

249430

Hom.:

AF XY:

0.000111

AC XY:

AN XY:

135336

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.00

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:

0.000212

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000267

AC:

391

AN:

1461846

Hom.:

Cov.:

AF XY:

0.000267

AC XY:

194

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

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:

0.000339

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.0000985

AC:

AN:

152262

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000268

Hom.:

Bravo

AF:

0.000106

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000244

AC:

ExAC

AF:

0.000116

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000237

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 15, 2021

The c.857A>T (p.N286I) alteration is located in exon 10 (coding exon 9) of the NAP1L4 gene. This alteration results from a A to T substitution at nucleotide position 857, causing the asparagine (N) at amino acid position 286 to be replaced by an isoleucine (I). 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

0.28

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

.;T;.

Eigen

Benign

-0.096

Eigen_PC

Benign

-0.050

FATHMM_MKL

Pathogenic

0.98

M_CAP

Benign

0.019

MetaRNN

Uncertain

0.66

D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

M;M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.63

PROVEAN

Pathogenic

-7.2

.;D;D

REVEL

Benign

0.22

Sift

Uncertain

0.012

.;D;D

Sift4G

Uncertain

0.043

D;D;D

Polyphen

0.13

.;B;.

Vest4

0.71

MVP

0.50

MPC

0.59

ClinPred

0.26

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.47

gMVP

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

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