Genetic Variant NM_001007531.3:c.711G>A (chr6-28260082-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001007531.3(NKAPL):c.711G>A(p.Lys237Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0412 in 1,578,566 control chromosomes in the GnomAD database, including 1,630 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.046 ( 186 hom., cov: 32)

Exomes 𝑓: 0.041 ( 1444 hom. )

Consequence

NKAPL
NM_001007531.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.27

Publications

9 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP7

Synonymous conserved (PhyloP=1.27 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NKAPL	NM_001007531.3 link	c.711G>A	p.Lys237Lys	synonymous_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.711G>A	p.Lys237Lys	synonymous_variant	Exon 1 of 1	6	NM_001007531.3	ENSP00000345716.3		Q5M9Q1

Frequencies

GnomAD3 genomes

AF:

0.0461

AC:

7004

AN:

151946

Hom.:

184

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0576

Gnomad AMI

AF:

0.0570

Gnomad AMR

AF:

0.0455

Gnomad ASJ

AF:

0.0453

Gnomad EAS

AF:

0.0718

Gnomad SAS

AF:

0.0803

Gnomad FIN

AF:

0.0275

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0375

Gnomad OTH

AF:

0.0455

GnomAD2 exomes

AF:

0.0449

AC:

9507

AN:

211676

AF XY:

0.0469

show subpopulations

Gnomad AFR exome

AF:

0.0556

Gnomad AMR exome

AF:

0.0381

Gnomad ASJ exome

AF:

0.0477

Gnomad EAS exome

AF:

0.0572

Gnomad FIN exome

AF:

0.0253

Gnomad NFE exome

AF:

0.0372

Gnomad OTH exome

AF:

0.0394

GnomAD4 exome

AF:

0.0407

AC:

58017

AN:

1426502

Hom.:

1444

Cov.:

AF XY:

0.0422

AC XY:

29908

AN XY:

708766

show subpopulations

African (AFR)

AF:

0.0568

AC:

1768

AN:

31110

American (AMR)

AF:

0.0409

AC:

1378

AN:

33686

Ashkenazi Jewish (ASJ)

AF:

0.0466

AC:

1126

AN:

24164

East Asian (EAS)

AF:

0.0898

AC:

3552

AN:

39570

South Asian (SAS)

AF:

0.0855

AC:

6748

AN:

78940

European-Finnish (FIN)

AF:

0.0275

AC:

1442

AN:

52500

Middle Eastern (MID)

AF:

0.0637

AC:

355

AN:

5574

European-Non Finnish (NFE)

AF:

0.0356

AC:

39284

AN:

1102176

Other (OTH)

AF:

0.0402

AC:

2364

AN:

58782

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

2937

5874

8812

11749

14686

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1530

3060

4590

6120

7650

<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:

0.0462

AC:

7022

AN:

152064

Hom.:

186

Cov.:

AF XY:

0.0456

AC XY:

3394

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.0577

AC:

2393

AN:

41488

American (AMR)

AF:

0.0454

AC:

693

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0453

AC:

157

AN:

3464

East Asian (EAS)

AF:

0.0716

AC:

371

AN:

5184

South Asian (SAS)

AF:

0.0824

AC:

397

AN:

4816

European-Finnish (FIN)

AF:

0.0275

AC:

290

AN:

10556

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0375

AC:

2547

AN:

67962

Other (OTH)

AF:

0.0455

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

325

650

976

1301

1626

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

258

344

430

<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:

0.0222

Hom.:

Bravo

AF:

0.0467

Asia WGS

AF:

0.0550

AC:

190

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

8.3

(source)

DANN

Benign

0.35

PhyloP100

1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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