Genetic Variant NM_001007531.3:c.484C>T (chr6-28259855-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001007531.3(NKAPL):c.484C>T(p.His162Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0487 in 1,613,944 control chromosomes in the GnomAD database, including 2,390 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.053 ( 263 hom., cov: 32)

Exomes 𝑓: 0.048 ( 2127 hom. )

Consequence

NKAPL
NM_001007531.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.224

Publications

21 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019891262).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NKAPL	NM_001007531.3 link	c.484C>T	p.His162Tyr	missense_variant	Exon 1 of 1	ENST00000343684.4	NP_001007532.1	Q5M9Q1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NKAPL	ENST00000343684.4 link	c.484C>T	p.His162Tyr	missense_variant	Exon 1 of 1	6	NM_001007531.3	ENSP00000345716.3		Q5M9Q1

Frequencies

GnomAD3 genomes

AF:

0.0533

AC:

8107

AN:

152014

Hom.:

263

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0567

Gnomad AMI

AF:

0.0198

Gnomad AMR

AF:

0.0845

Gnomad ASJ

AF:

0.0470

Gnomad EAS

AF:

0.118

Gnomad SAS

AF:

0.0839

Gnomad FIN

AF:

0.0248

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0423

Gnomad OTH

AF:

0.0641

GnomAD2 exomes

AF:

0.0591

AC:

14825

AN:

251006

AF XY:

0.0594

show subpopulations

Gnomad AFR exome

AF:

0.0552

Gnomad AMR exome

AF:

0.0857

Gnomad ASJ exome

AF:

0.0469

Gnomad EAS exome

AF:

0.117

Gnomad FIN exome

AF:

0.0313

Gnomad NFE exome

AF:

0.0415

Gnomad OTH exome

AF:

0.0539

GnomAD4 exome

AF:

0.0482

AC:

70518

AN:

1461812

Hom.:

2127

Cov.:

AF XY:

0.0495

AC XY:

35961

AN XY:

727206

show subpopulations

African (AFR)

AF:

0.0563

AC:

1884

AN:

33476

American (AMR)

AF:

0.0833

AC:

3724

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0474

AC:

1240

AN:

26136

East Asian (EAS)

AF:

0.147

AC:

5842

AN:

39700

South Asian (SAS)

AF:

0.0851

AC:

7340

AN:

86254

European-Finnish (FIN)

AF:

0.0307

AC:

1637

AN:

53380

Middle Eastern (MID)

AF:

0.0468

AC:

270

AN:

5768

European-Non Finnish (NFE)

AF:

0.0410

AC:

45642

AN:

1111984

Other (OTH)

AF:

0.0487

AC:

2939

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

3803

7607

11410

15214

19017

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1864

3728

5592

7456

9320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0533

AC:

8109

AN:

152132

Hom.:

263

Cov.:

AF XY:

0.0539

AC XY:

4008

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.0565

AC:

2342

AN:

41468

American (AMR)

AF:

0.0845

AC:

1293

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0470

AC:

163

AN:

3470

East Asian (EAS)

AF:

0.118

AC:

611

AN:

5178

South Asian (SAS)

AF:

0.0845

AC:

407

AN:

4814

European-Finnish (FIN)

AF:

0.0248

AC:

263

AN:

10584

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0423

AC:

2874

AN:

68008

Other (OTH)

AF:

0.0630

AC:

133

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

395

791

1186

1582

1977

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

200

300

400

500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0464

Hom.:

826

Bravo

AF:

0.0581

TwinsUK

AF:

0.0423

AC:

157

ALSPAC

AF:

0.0459

AC:

177

ESP6500AA

AF:

0.0493

AC:

217

ESP6500EA

AF:

0.0435

AC:

374

ExAC

AF:

0.0571

AC:

6928

Asia WGS

AF:

0.0870

AC:

302

AN:

3478

EpiCase

AF:

0.0413

EpiControl

AF:

0.0429

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.7

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.0041

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.37

MetaRNN

Benign

0.0020

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.69

PhyloP100

0.22

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.0

REVEL

Benign

0.013

Sift

Benign

0.034

Sift4G

Benign

0.15

Polyphen

0.39

Vest4

0.044

MPC

0.50

ClinPred

0.000022

GERP RS

-1.6

Varity_R

0.050

gMVP

0.017

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over