Genetic Variant NM_198465.4:c.607A>T (chrX-105898610-A-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_198465.4(NRK):c.607A>T(p.Ser203Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000534 in 1,198,173 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 15 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.000054 ( 0 hom. 15 hem. )

Consequence

NRK
NM_198465.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.89

Publications

0 publications found

Variant links:

Genes affected

NRK (HGNC:25391): (Nik related kinase) The mouse ortholog of this gene encodes a protein kinase required for JNK activation. The encoded protein may be involved in the induction of actin polymerization in late embryogenesis.[provided by RefSeq, Jun 2010]

NRK 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=0.075427294).

BS2

High Hemizygotes in GnomAdExome4 at 15 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198465.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRK	NM_198465.4	MANE Select	c.607A>T	p.Ser203Cys	missense	Exon 8 of 29	NP_940867.2	Q7Z2Y5-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NRK	ENST00000243300.14	TSL:1 MANE Select	c.607A>T	p.Ser203Cys	missense	Exon 8 of 29	ENSP00000434830.1	Q7Z2Y5-1
NRK	ENST00000882684.1		c.607A>T	p.Ser203Cys	missense	Exon 8 of 28	ENSP00000552743.1
NRK	ENST00000882683.1		c.607A>T	p.Ser203Cys	missense	Exon 8 of 28	ENSP00000552742.1

Frequencies

GnomAD3 genomes

AF:

0.0000448

AC:

AN:

111483

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000479

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000289

AC:

AN:

166251

AF XY:

0.000187

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00175

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000979

GnomAD4 exome

AF:

0.0000543

AC:

AN:

1086690

Hom.:

Cov.:

AF XY:

0.0000425

AC XY:

AN XY:

352910

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26146

American (AMR)

AF:

0.00163

AC:

AN:

34453

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19234

East Asian (EAS)

AF:

0.00

AC:

AN:

29891

South Asian (SAS)

AF:

0.00

AC:

AN:

52278

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40311

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4109

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

834543

Other (OTH)

AF:

0.0000656

AC:

AN:

45725

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0000448

AC:

AN:

111483

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33655

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30585

American (AMR)

AF:

0.000479

AC:

AN:

10441

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2651

East Asian (EAS)

AF:

0.00

AC:

AN:

3541

South Asian (SAS)

AF:

0.00

AC:

AN:

2647

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6040

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53157

Other (OTH)

AF:

0.00

AC:

AN:

1496

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

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:

0.0000907

ExAC

AF:

0.000224

AC:

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

Uncertain

0.36

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.32

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.072

MetaRNN

Benign

0.075

MetaSVM

Benign

-0.32

MutationAssessor

Benign

2.0

PhyloP100

7.9

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-3.3

REVEL

Uncertain

0.46

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.25

MutPred

0.61

Loss of disorder (P = 6e-04)

MVP

0.81

ClinPred

0.15

GERP RS

4.6

Varity_R

0.49

gMVP

0.81

Mutation Taster

=79/21

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