Genetic Variant NKAIN4:p.Arg110His (chr20-63247720-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_152864.4(NKAIN4):c.329G>A(p.Arg110His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000319 in 1,506,656 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000033 ( 1 hom. )

Consequence

NKAIN4
NM_152864.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.59

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017950803).

BP6

Variant 20-63247720-C-T is Benign according to our data. Variant chr20-63247720-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2599702.Status of the report is criteria_provided_single_submitter, 1 stars.

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.329G>A	p.Arg110His	missense	Exon 4 of 7	NP_690603.3
NKAIN4	NM_001363747.1		c.143G>A	p.Arg48His	missense	Exon 4 of 7	NP_001350676.1	A6NNM2
NKAIN4	NM_001363718.1		c.143G>A	p.Arg48His	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.329G>A	p.Arg110His	missense	Exon 4 of 7	ENSP00000359340.3	Q8IVV8
NKAIN4	ENST00000370317.3	TSL:5	c.119G>A	p.Arg40His	missense	Exon 2 of 6	ENSP00000359341.3	J9JIE8
NKAIN4	ENST00000370307.6	TSL:5	c.143G>A	p.Arg48His	missense	Exon 4 of 7	ENSP00000359330.2	A6NNM2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152224

Hom.:

Cov.:

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000823

AC:

AN:

121466

AF XY:

0.0000633

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000213

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000332

AC:

AN:

1354432

Hom.:

Cov.:

AF XY:

0.0000407

AC XY:

AN XY:

663232

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30226

American (AMR)

AF:

0.0000342

AC:

AN:

29242

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22690

East Asian (EAS)

AF:

0.0000284

AC:

AN:

35152

South Asian (SAS)

AF:

0.000402

AC:

AN:

72112

European-Finnish (FIN)

AF:

0.0000214

AC:

AN:

46812

Middle Eastern (MID)

AF:

0.000184

AC:

AN:

5422

European-Non Finnish (NFE)

AF:

0.00000852

AC:

AN:

1056812

Other (OTH)

AF:

0.0000536

AC:

AN:

55964

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

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:

0.0000197

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41454

American (AMR)

AF:

0.00

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

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:

0.00

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000573

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.059

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.74

CADD

Benign

5.4

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.0060

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.78

M_CAP

Benign

0.0061

MetaRNN

Benign

0.018

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-1.9

PhyloP100

2.6

PrimateAI

Uncertain

0.54

PROVEAN

Benign

4.0

REVEL

Benign

0.065

Sift

Benign

0.69

Sift4G

Benign

0.71

Polyphen

0.0010

Vest4

0.14

MutPred

0.48

Loss of MoRF binding (P = 0.0331)

MVP

0.030

MPC

0.0076

ClinPred

0.023

GERP RS

2.4

Varity_R

0.019

gMVP

0.16

Mutation Taster

=90/10

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