chr6-124283138-C-A

Position:

• chr6-124283138-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001040214.3(NKAIN2):​c.188C>A​(p.Thr63Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NKAIN2 NM_001040214.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.46

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NKAIN2	NM_001040214.3	c.188C>A	p.Thr63Lys	missense_variant	2/7	ENST00000368417.6	NP_001035304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NKAIN2	ENST00000368417.6	c.188C>A	p.Thr63Lys	missense_variant	2/7	5	NM_001040214.3	ENSP00000357402	P1
NKAIN2	ENST00000368416.5	c.188C>A	p.Thr63Lys	missense_variant	2/4	1		ENSP00000357401
NKAIN2	ENST00000476571.1	n.312C>A		non_coding_transcript_exon_variant	3/5	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1448988 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 721814

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 28, 2023

The c.188C>A (p.T63K) alteration is located in exon 2 (coding exon 2) of the NKAIN2 gene. This alteration results from a C to A substitution at nucleotide position 188, causing the threonine (T) at amino acid position 63 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	.;T;.;.
Eigen	Benign	0.023
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.78	T;T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.46	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;L;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-2.6	D;N;.;.
REVEL	Benign	0.15
Sift	Benign	0.13	T;D;.;.
Sift4G	Uncertain	0.0080	D;D;D;D
Polyphen		1.0	D;B;B;.
Vest4		0.44
MutPred		0.73		Gain of MoRF binding (P = 0.0256);Gain of MoRF binding (P = 0.0256);.;.;
MVP		0.41
MPC		1.2
ClinPred		0.97	D
GERP RS		4.8
Varity_R		0.52
gMVP		0.89

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-124604284;