Genetic Variant NRK:p.His368His (chrX-105908745-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_198465.4(NRK):c.1104C>T(p.His368His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00017 in 1,197,414 control chromosomes in the GnomAD database, including 1 homozygotes. There are 56 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00068 ( 0 hom., 16 hem., cov: 23)

Exomes 𝑓: 0.00012 ( 1 hom. 40 hem. )

Consequence

NRK
NM_198465.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.309

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant X-105908745-C-T is Benign according to our data. Variant chrX-105908745-C-T is described in ClinVar as Benign. ClinVar VariationId is 723211.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.309 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 16 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.1104C>T	p.His368His	synonymous	Exon 13 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.1104C>T	p.His368His	synonymous	Exon 13 of 29	ENSP00000434830.1	Q7Z2Y5-1
NRK	ENST00000882684.1		c.1104C>T	p.His368His	synonymous	Exon 13 of 28	ENSP00000552743.1
NRK	ENST00000882683.1		c.1104C>T	p.His368His	synonymous	Exon 13 of 28	ENSP00000552742.1

Frequencies

GnomAD3 genomes

AF:

0.000679

AC:

AN:

111971

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00211

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000189

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00170

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00133

GnomAD2 exomes

AF:

0.000321

AC:

AN:

168056

AF XY:

0.000319

show subpopulations

Gnomad AFR exome

AF:

0.00213

Gnomad AMR exome

AF:

0.000273

Gnomad ASJ exome

AF:

0.000160

Gnomad EAS exome

AF:

0.00129

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000118

AC:

128

AN:

1085389

Hom.:

Cov.:

AF XY:

0.000113

AC XY:

AN XY:

353301

show subpopulations

African (AFR)

AF:

0.00272

AC:

AN:

26122

American (AMR)

AF:

0.000322

AC:

AN:

34207

Ashkenazi Jewish (ASJ)

AF:

0.0000535

AC:

AN:

18708

East Asian (EAS)

AF:

0.000901

AC:

AN:

29963

South Asian (SAS)

AF:

0.0000191

AC:

AN:

52442

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40200

Middle Eastern (MID)

AF:

0.000740

AC:

AN:

4052

European-Non Finnish (NFE)

AF:

0.00000719

AC:

AN:

834159

Other (OTH)

AF:

0.000176

AC:

AN:

45536

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

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:

0.000678

AC:

AN:

112025

Hom.:

Cov.:

AF XY:

0.000468

AC XY:

AN XY:

34207

show subpopulations

African (AFR)

AF:

0.00211

AC:

AN:

30859

American (AMR)

AF:

0.000189

AC:

AN:

10580

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2647

East Asian (EAS)

AF:

0.00170

AC:

AN:

3525

South Asian (SAS)

AF:

0.00

AC:

AN:

2696

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6077

Middle Eastern (MID)

AF:

0.00

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53217

Other (OTH)

AF:

0.00131

AC:

AN:

1525

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.000521

Hom.:

Bravo

AF:

0.000918

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

0.52

(source)

DANN

Benign

0.51

PhyloP100

-0.31

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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