Genetic Variant NKAIN4:p.Gly125Arg (chr20-63247676-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_152864.4(NKAIN4):c.373G>A(p.Gly125Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000376 in 1,542,728 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000037 ( 1 hom. )

Consequence

NKAIN4
NM_152864.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.105

Publications

1 publications found

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]

NKAIN4 links:

LOC124904950 (HGNC:):

LOC124904950 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0413993).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152864.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NKAIN4	NM_152864.4	MANE Select	c.373G>A	p.Gly125Arg	missense	Exon 4 of 7	NP_690603.3
NKAIN4	NM_001363747.1		c.187G>A	p.Gly63Arg	missense	Exon 4 of 7	NP_001350676.1	A6NNM2
NKAIN4	NM_001363718.1		c.187G>A	p.Gly63Arg	missense	Exon 4 of 6	NP_001350647.1	J3JS66

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NKAIN4	ENST00000370316.8	TSL:1 MANE Select	c.373G>A	p.Gly125Arg	missense	Exon 4 of 7	ENSP00000359340.3	Q8IVV8
NKAIN4	ENST00000370317.3	TSL:5	c.163G>A	p.Gly55Arg	missense	Exon 2 of 6	ENSP00000359341.3	J9JIE8
NKAIN4	ENST00000370307.6	TSL:5	c.187G>A	p.Gly63Arg	missense	Exon 4 of 7	ENSP00000359330.2	A6NNM2

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000808

AC:

AN:

148556

AF XY:

0.0000891

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000858

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000824

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000367

AC:

AN:

1390496

Hom.:

Cov.:

AF XY:

0.0000336

AC XY:

AN XY:

685072

show subpopulations

African (AFR)

AF:

0.0000955

AC:

AN:

31414

American (AMR)

AF:

0.0000576

AC:

AN:

34710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24782

East Asian (EAS)

AF:

0.00112

AC:

AN:

35600

South Asian (SAS)

AF:

0.00

AC:

AN:

77666

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47878

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5638

European-Non Finnish (NFE)

AF:

0.00000558

AC:

AN:

1075198

Other (OTH)

AF:

0.00

AC:

AN:

57610

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41460

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000770

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68028

Other (OTH)

AF:

0.000478

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.546

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000285

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000430

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.78

CADD

Benign

3.0

(source)

DANN

Benign

0.33

DEOGEN2

Benign

0.018

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.58

M_CAP

Benign

0.0031

MetaRNN

Benign

0.041

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.080

PhyloP100

0.10

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.049

Sift

Benign

0.67

Sift4G

Benign

0.81

Polyphen

0.036

Vest4

0.080

MutPred

0.55

Gain of solvent accessibility (P = 1e-04)

MVP

0.18

MPC

0.0080

ClinPred

0.029

GERP RS

-1.0

Varity_R

0.063

gMVP

0.10

Mutation Taster

=83/17

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over