rs10499129

Variant names:

• chr6-124613061-A-G
• rs10499129
• NM_001040214.3:c.274-45125A>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.274-45125A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,138 control chromosomes in the GnomAD database, including 1,456 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 0.13 (1456 hom., cov: 32)
• Consequence: NKAIN2 NM_001040214.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88
• Publications: 8 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NKAIN2	NM_001040214.3	c.274-45125A>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.274-45125A>G		intron_variant	Intron 3 of 6	5	NM_001040214.3	ENSP00000357402.1
NKAIN2	ENST00000368416.5	c.274-45125A>G		intron_variant	Intron 3 of 3	1		ENSP00000357401.1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20076 AN: 152022 Hom.: 1452 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.132 AC: 20094 AN: 152138 Hom.: 1456 Cov.: 32 AF XY: 0.135 AC XY: 10036 AN XY: 74384

African (AFR) AF: 0.171 AC: 7090 AN: 41498

American (AMR) AF: 0.137 AC: 2099 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 402 AN: 3470

East Asian (EAS) AF: 0.166 AC: 855 AN: 5156

South Asian (SAS) AF: 0.222 AC: 1072 AN: 4822

European-Finnish (FIN) AF: 0.106 AC: 1122 AN: 10598

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7103 AN: 67998

Other (OTH) AF: 0.148 AC: 313 AN: 2112

Alfa AF: 0.114 Hom.: 1738

Bravo AF: 0.133

Asia WGS AF: 0.180 AC: 627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.011
DANN	Benign	0.28
PhyloP100		-1.9
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: rs10499129; hg19: chr6-124934207; COSMIC: COSV63686991;