Variant rs1635 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001007531.3(NKAPL):c.455C>A(p.Thr152Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0795 in 1,614,030 control chromosomes in the GnomAD database, including 9,995 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.14 ( 2381 hom., cov: 32)

Exomes 𝑓: 0.073 ( 7614 hom. )

Consequence

NKAPL
NM_001007531.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.03

Variant links:

Genes affected

NKAPL (HGNC:21584): (NFKB activating protein like) Predicted to enable chromatin binding activity. Predicted to be involved in regulation of gene expression. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

NKAPL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016289353).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NKAPL	NM_001007531.3 linkuse as main transcript	c.455C>A	p.Thr152Asn	missense_variant	1/1	ENST00000343684.4	NP_001007532.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NKAPL	ENST00000343684.4 linkuse as main transcript	c.455C>A	p.Thr152Asn	missense_variant	1/1		NM_001007531.3	ENSP00000345716	P1

Frequencies

GnomAD3 genomes

AF:

0.139

AC:

21174

AN:

152054

Hom.:

2366

Cov.:

show subpopulations

Gnomad AFR

AF:

0.284

Gnomad AMI

AF:

0.0615

Gnomad AMR

AF:

0.152

Gnomad ASJ

AF:

0.0905

Gnomad EAS

AF:

0.346

Gnomad SAS

AF:

0.160

Gnomad FIN

AF:

0.0441

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.0499

Gnomad OTH

AF:

0.136

GnomAD3 exomes

AF:

0.118

AC:

29563

AN:

251212

Hom.:

2956

AF XY:

0.113

AC XY:

15306

AN XY:

135818

show subpopulations

Gnomad AFR exome

AF:

0.287

Gnomad AMR exome

AF:

0.159

Gnomad ASJ exome

AF:

0.103

Gnomad EAS exome

AF:

0.365

Gnomad SAS exome

AF:

0.151

Gnomad FIN exome

AF:

0.0411

Gnomad NFE exome

AF:

0.0496

Gnomad OTH exome

AF:

0.0816

GnomAD4 exome

AF:

0.0733

AC:

107102

AN:

1461858

Hom.:

7614

Cov.:

AF XY:

0.0752

AC XY:

54721

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.294

Gnomad4 AMR exome

AF:

0.157

Gnomad4 ASJ exome

AF:

0.0970

Gnomad4 EAS exome

AF:

0.366

Gnomad4 SAS exome

AF:

0.156

Gnomad4 FIN exome

AF:

0.0424

Gnomad4 NFE exome

AF:

0.0463

Gnomad4 OTH exome

AF:

0.0880

GnomAD4 genome

AF:

0.140

AC:

21230

AN:

152172

Hom.:

2381

Cov.:

AF XY:

0.140

AC XY:

10449

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.284

Gnomad4 AMR

AF:

0.151

Gnomad4 ASJ

AF:

0.0905

Gnomad4 EAS

AF:

0.345

Gnomad4 SAS

AF:

0.162

Gnomad4 FIN

AF:

0.0441

Gnomad4 NFE

AF:

0.0499

Gnomad4 OTH

AF:

0.135

Alfa

AF:

0.0750

Hom.:

1945

Bravo

AF:

0.155

TwinsUK

AF:

0.0378

AC:

140

ALSPAC

AF:

0.0488

AC:

188

ESP6500AA

AF:

0.279

AC:

1231

ESP6500EA

AF:

0.0537

AC:

462

ExAC

AF:

0.118

AC:

14295

Asia WGS

AF:

0.173

AC:

599

AN:

3478

EpiCase

AF:

0.0513

EpiControl

AF:

0.0516

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

4.2

DANN

Benign

0.69

DEOGEN2

Benign

0.026

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.58

MetaRNN

Benign

0.0016

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

0.051

PrimateAI

Benign

0.28

PROVEAN

Benign

-2.3

REVEL

Benign

0.13

Sift

Benign

0.096

Sift4G

Uncertain

0.057

Polyphen

0.0030

Vest4

0.023

MPC

0.49

ClinPred

0.0065

GERP RS

-0.57

Varity_R

0.14

gMVP

0.13

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over