rs3734564

chr6-28260082-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001007531.3(NKAPL):c.711G>A(p.Lys237=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
NKAPL	NM_001007531.3	c.711G>A	p.Lys237=	synonymous_variant	1/1	ENST00000343684.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NKAPL	ENST00000343684.4	c.711G>A	p.Lys237=	synonymous_variant	1/1		NM_001007531.3	P1

Frequencies

GnomAD3 genomes AF: 0.0461 AC: 7004 AN: 151946 Hom.: 184 Cov.: 32

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

GnomAD3 exomes AF: 0.0449 AC: 9507 AN: 211676 Hom.: 273 AF XY: 0.0469 AC XY: 5409 AN XY: 115366

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 SAS exome AF: 0.0861

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.: 34 AF XY: 0.0422 AC XY: 29908 AN XY: 708766

Gnomad4 AFR exome AF: 0.0568

Gnomad4 AMR exome AF: 0.0409

Gnomad4 ASJ exome AF: 0.0466

Gnomad4 EAS exome AF: 0.0898

Gnomad4 SAS exome AF: 0.0855

Gnomad4 FIN exome AF: 0.0275

Gnomad4 NFE exome AF: 0.0356

Gnomad4 OTH exome AF: 0.0402

GnomAD4 genome AF: 0.0462 AC: 7022 AN: 152064 Hom.: 186 Cov.: 32 AF XY: 0.0456 AC XY: 3394 AN XY: 74354

Gnomad4 AFR AF: 0.0577

Gnomad4 AMR AF: 0.0454

Gnomad4 ASJ AF: 0.0453

Gnomad4 EAS AF: 0.0716

Gnomad4 SAS AF: 0.0824

Gnomad4 FIN AF: 0.0275

Gnomad4 NFE AF: 0.0375

Gnomad4 OTH AF: 0.0455

Alfa AF: 0.0221 Hom.: 61

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
Dann	Benign	0.35

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

Other links and lift over

dbSNP: rs3734564; hg19: chr6-28227860;