Variant 6-124823221-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001040214.3(NKAIN2):c.619T>C(p.Ser207Pro) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000138 in 1,444,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

NKAIN2
NM_001040214.3 missense, splice_region

Scores

Splicing: ADA: 0.3946

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.85

Variant links:

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]

NKAIN2 links:

RNF217-AS1 (HGNC:50866): (RNF217 antisense RNA 1 (head to head))

RNF217-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4018992).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NKAIN2	NM_001040214.3 linkuse as main transcript	c.619T>C	p.Ser207Pro	missense_variant, splice_region_variant	7/7	ENST00000368417.6	NP_001035304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NKAIN2	ENST00000368417.6 linkuse as main transcript	c.619T>C	p.Ser207Pro	missense_variant, splice_region_variant	7/7	5	NM_001040214.3	ENSP00000357402	P1	Q5VXU1-1
RNF217-AS1	ENST00000663792.1 linkuse as main transcript	n.536-36691A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1444582

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719856

show subpopulations

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:

0.0000334

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 23, 2024

The c.619T>C (p.S207P) alteration is located in exon 7 (coding exon 7) of the NKAIN2 gene. This alteration results from a T to C substitution at nucleotide position 619, causing the serine (S) at amino acid position 207 to be replaced by a proline (P). 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

Benign

0.30

BayesDel_addAF

Benign

-0.0012

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.018

T;.

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.70

T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.40

T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

0.51

N;.

MutationTaster

Benign

0.97

PrimateAI

Uncertain

0.77

PROVEAN

Benign

0.020

N;.

REVEL

Benign

0.26

Sift

Uncertain

0.0070

D;.

Sift4G

Benign

0.23

T;T

Polyphen

0.93

P;D

Vest4

0.47

MutPred

0.53

Gain of loop (P = 0.0312);.;

MVP

0.40

MPC

0.53

ClinPred

0.77

GERP RS

5.9

Varity_R

0.31

gMVP

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.39

dbscSNV1_RF

Benign

0.50

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over