6-123804242-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001040214.3(NKAIN2):ā€‹c.42T>Gā€‹(p.Cys14Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000027 ( 0 hom. )

Consequence

NKAIN2
NM_001040214.3 missense

Scores

6
7
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.80
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.935

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NKAIN2NM_001040214.3 linkuse as main transcriptc.42T>G p.Cys14Trp missense_variant 1/7 ENST00000368417.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NKAIN2ENST00000368417.6 linkuse as main transcriptc.42T>G p.Cys14Trp missense_variant 1/75 NM_001040214.3 P1Q5VXU1-1
NKAIN2ENST00000368416.5 linkuse as main transcriptc.42T>G p.Cys14Trp missense_variant 1/41 Q5VXU1-2
NKAIN2ENST00000476571.1 linkuse as main transcriptn.102T>G non_coding_transcript_exon_variant 1/55

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000803
AC:
2
AN:
249142
Hom.:
0
AF XY:
0.00000741
AC XY:
1
AN XY:
134914
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000179
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461550
Hom.:
0
Cov.:
30
AF XY:
0.00000413
AC XY:
3
AN XY:
727128
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:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000658
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 submitterclinical testingAmbry GeneticsJul 05, 2023The c.42T>G (p.C14W) alteration is located in exon 1 (coding exon 1) of the NKAIN2 gene. This alteration results from a T to G substitution at nucleotide position 42, causing the cysteine (C) at amino acid position 14 to be replaced by a tryptophan (W). 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
Pathogenic
0.97
BayesDel_addAF
Uncertain
0.028
T
BayesDel_noAF
Benign
-0.20
CADD
Uncertain
24
DANN
Uncertain
0.98
DEOGEN2
Benign
0.18
.;T
Eigen
Uncertain
0.53
Eigen_PC
Uncertain
0.45
FATHMM_MKL
Benign
0.67
D
LIST_S2
Uncertain
0.91
D;D
M_CAP
Benign
0.068
D
MetaRNN
Pathogenic
0.94
D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.4
M;M
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Pathogenic
0.82
D
PROVEAN
Pathogenic
-5.7
D;D
REVEL
Uncertain
0.30
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0010
D;D
Polyphen
1.0
D;P
Vest4
0.88
MutPred
0.83
Gain of catalytic residue at I11 (P = 0.2421);Gain of catalytic residue at I11 (P = 0.2421);
MVP
0.42
MPC
1.0
ClinPred
0.99
D
GERP RS
4.2
Varity_R
0.87
gMVP
0.86

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs777170271; hg19: chr6-124125387; API