6-124440303-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001040214.3(NKAIN2):c.273+84956C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 151,870 control chromosomes in the GnomAD database, including 7,646 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 0.30 (7646 hom., cov: 31)
• Consequence: NKAIN2 NM_001040214.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340

Genes affected

NKAIN2 (HGNC:16443): (sodium/potassium transporting ATPase interacting 2) This gene encodes a transmembrane protein that interacts with the beta subunit of a sodium/potassium-transporting ATPase. A chromosomal translocation involving this gene is a cause of lymphoma. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NKAIN2	NM_001040214.3	c.273+84956C>T		intron_variant		ENST00000368417.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NKAIN2	ENST00000368417.6	c.273+84956C>T		intron_variant		5	NM_001040214.3	P1
NKAIN2	ENST00000368416.5	c.273+84956C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46149 AN: 151752 Hom.: 7618 Cov.: 31

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.272

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.304 AC: 46224 AN: 151870 Hom.: 7646 Cov.: 31 AF XY: 0.298 AC XY: 22113 AN XY: 74226

Gnomad4 AFR AF: 0.433

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.242

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.279

Alfa AF: 0.169 Hom.: 317

Bravo AF: 0.310

Asia WGS AF: 0.260 AC: 903 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	1.3
Dann	Benign	0.63

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: rs590944; hg19: chr6-124761449; COSMIC: COSV63650107;