6-124361442-A-G

Variant names:

• chr6-124361442-A-G
• rs6940582
• NM_001040214.3:c.273+6095A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001040214.3(NKAIN2):​c.273+6095A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.86 in 151,980 control chromosomes in the GnomAD database, including 56,520 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 0.86 (56520 hom., cov: 31)
• Consequence: NKAIN2 NM_001040214.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.665
• Publications: 2 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NKAIN2	NM_001040214.3	c.273+6095A>G		intron_variant	Intron 3 of 6	ENST00000368417.6	NP_001035304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NKAIN2	ENST00000368417.6	c.273+6095A>G		intron_variant	Intron 3 of 6	5	NM_001040214.3	ENSP00000357402.1
NKAIN2	ENST00000368416.5	c.273+6095A>G		intron_variant	Intron 3 of 3	1		ENSP00000357401.1
NKAIN2	ENST00000476571.1	n.397+6095A>G		intron_variant	Intron 4 of 4	5

Frequencies

GnomAD3 genomes AF: 0.860 AC: 130541 AN: 151862 Hom.: 56459 Cov.: 31

Gnomad AFR AF: 0.957

Gnomad AMI AF: 0.870

Gnomad AMR AF: 0.868

Gnomad ASJ AF: 0.867

Gnomad EAS AF: 0.808

Gnomad SAS AF: 0.838

Gnomad FIN AF: 0.830

Gnomad MID AF: 0.831

Gnomad NFE AF: 0.808

Gnomad OTH AF: 0.864

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

GnomAD4 genome AF: 0.860 AC: 130658 AN: 151980 Hom.: 56520 Cov.: 31 AF XY: 0.862 AC XY: 64013 AN XY: 74266

African (AFR) AF: 0.957 AC: 39755 AN: 41540

American (AMR) AF: 0.868 AC: 13241 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.867 AC: 3008 AN: 3468

East Asian (EAS) AF: 0.808 AC: 4161 AN: 5152

South Asian (SAS) AF: 0.839 AC: 4043 AN: 4820

European-Finnish (FIN) AF: 0.830 AC: 8772 AN: 10572

Middle Eastern (MID) AF: 0.836 AC: 244 AN: 292

European-Non Finnish (NFE) AF: 0.808 AC: 54823 AN: 67856

Other (OTH) AF: 0.862 AC: 1818 AN: 2110

Alfa AF: 0.842 Hom.: 7005

Bravo AF: 0.869

Asia WGS AF: 0.820 AC: 2842 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.60
DANN	Benign	0.39
PhyloP100		-0.67
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6940582; hg19: chr6-124682588; COSMIC: COSV63649805;