6-123804242-T-G
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001040214.3(NKAIN2):āc.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
NM_001040214.3 missense
Scores
6
7
6
Clinical Significance
Conservation
PhyloP100: 1.80
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 |
---|---|---|---|---|---|---|---|
NKAIN2 | NM_001040214.3 | c.42T>G | p.Cys14Trp | missense_variant | 1/7 | ENST00000368417.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NKAIN2 | ENST00000368417.6 | c.42T>G | p.Cys14Trp | missense_variant | 1/7 | 5 | NM_001040214.3 | P1 | |
NKAIN2 | ENST00000368416.5 | c.42T>G | p.Cys14Trp | missense_variant | 1/4 | 1 | |||
NKAIN2 | ENST00000476571.1 | n.102T>G | non_coding_transcript_exon_variant | 1/5 | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000803 AC: 2AN: 249142Hom.: 0 AF XY: 0.00000741 AC XY: 1AN XY: 134914
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461550Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 727128
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GnomAD4 genome Cov.: 32
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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 | Jul 05, 2023 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;P
Vest4
MutPred
Gain of catalytic residue at I11 (P = 0.2421);Gain of catalytic residue at I11 (P = 0.2421);
MVP
MPC
1.0
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at