6-123981398-C-G

Variant names:

• chr6-123981398-C-G
• rs12190776
• NM_001040214.3:c.54+177144C>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.54+177144C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,032 control chromosomes in the GnomAD database, including 4,837 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 0.24 (4837 hom., cov: 32)
• Consequence: NKAIN2 NM_001040214.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22
• Publications: 1 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NKAIN2	NM_001040214.3	c.54+177144C>G		intron_variant	Intron 1 of 6	ENST00000368417.6	NP_001035304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NKAIN2	ENST00000368417.6	c.54+177144C>G		intron_variant	Intron 1 of 6	5	NM_001040214.3	ENSP00000357402.1
NKAIN2	ENST00000368416.5	c.54+177144C>G		intron_variant	Intron 1 of 3	1		ENSP00000357401.1
NKAIN2	ENST00000476571.1	n.115-140480C>G		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36903 AN: 151914 Hom.: 4841 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.243 AC: 36906 AN: 152032 Hom.: 4837 Cov.: 32 AF XY: 0.244 AC XY: 18159 AN XY: 74296

African (AFR) AF: 0.158 AC: 6569 AN: 41484

American (AMR) AF: 0.205 AC: 3139 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 939 AN: 3470

East Asian (EAS) AF: 0.154 AC: 795 AN: 5174

South Asian (SAS) AF: 0.171 AC: 824 AN: 4818

European-Finnish (FIN) AF: 0.361 AC: 3801 AN: 10542

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.296 AC: 20108 AN: 67952

Other (OTH) AF: 0.218 AC: 459 AN: 2110

Alfa AF: 0.151 Hom.: 308

Bravo AF: 0.229

Asia WGS AF: 0.155 AC: 540 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.067
DANN	Benign	0.57
PhyloP100		-2.2
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: rs12190776; hg19: chr6-124302543; COSMIC: COSV63649218;