20-63244026-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152864.4(NKAIN4):​c.530G>A​(p.Ser177Asn) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,612,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

NKAIN4
NM_152864.4 missense, splice_region

Scores

2
5
9
Splicing: ADA: 0.006375
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.81
Variant links:
Genes affected
NKAIN4 (HGNC:16191): (sodium/potassium transporting ATPase interacting 4) NKAIN4 is a member of a family of mammalian proteins (see NKAIN1; MIM 612871) with similarity to Drosophila Nkain and interacts with the beta subunit of Na,K-ATPase (ATP1B1; MIM 182330) (Gorokhova et al., 2007 [PubMed 17606467]).[supplied by OMIM, Jun 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1899026).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NKAIN4NM_152864.4 linkuse as main transcriptc.530G>A p.Ser177Asn missense_variant, splice_region_variant 5/7 ENST00000370316.8 NP_690603.3 Q8IVV8B3KWY5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NKAIN4ENST00000370316.8 linkuse as main transcriptc.530G>A p.Ser177Asn missense_variant, splice_region_variant 5/71 NM_152864.4 ENSP00000359340.3 Q8IVV8

Frequencies

GnomAD3 genomes
AF:
0.0000328
AC:
5
AN:
152262
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000242
AC:
6
AN:
248334
Hom.:
0
AF XY:
0.0000223
AC XY:
3
AN XY:
134616
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:
0.0000535
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000212
AC:
31
AN:
1460562
Hom.:
0
Cov.:
30
AF XY:
0.0000220
AC XY:
16
AN XY:
726510
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000188
Gnomad4 NFE exome
AF:
0.0000252
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152380
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74518
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000540
Hom.:
0
Bravo
AF:
0.00000756
ExAC
AF:
0.0000412
AC:
5

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 27, 2024The c.530G>A (p.S177N) alteration is located in exon 5 (coding exon 5) of the NKAIN4 gene. This alteration results from a G to A substitution at nucleotide position 530, causing the serine (S) at amino acid position 177 to be replaced by an asparagine (N). 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
0.21
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
21
DANN
Uncertain
0.99
Eigen
Uncertain
0.45
Eigen_PC
Uncertain
0.31
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Benign
0.30
T
M_CAP
Uncertain
0.14
D
MetaRNN
Benign
0.19
T
MetaSVM
Benign
-0.59
T
PROVEAN
Benign
-0.090
N
REVEL
Benign
0.11
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
MVP
0.44
ClinPred
0.64
D
GERP RS
3.9

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.0064
dbscSNV1_RF
Benign
0.11
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: rs201583735; hg19: chr20-61875378; API