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

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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 id 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRK	NM_198465.4 link	c.1104C>T	p.His368His	synonymous_variant	Exon 13 of 29	ENST00000243300.14	NP_940867.2	Q7Z2Y5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NRK	ENST00000243300.14 link	c.1104C>T	p.His368His	synonymous_variant	Exon 13 of 29	1	NM_198465.4	ENSP00000434830.1	Q7Z2Y5-1
NRK	ENST00000428173.3 link	n.*1099C>T		non_coding_transcript_exon_variant	Exon 13 of 23	2		ENSP00000438378.2	F5H049
NRK	ENST00000428173.3 link	n.*1099C>T		3_prime_UTR_variant	Exon 13 of 23	2		ENSP00000438378.2	F5H049

Frequencies

GnomAD3 genomes

AF:

0.000679

AC:

AN:

111971

Hom.:

Cov.:

AF XY:

0.000469

AC XY:

AN XY:

34143

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

GnomAD3 exomes

AF:

0.000321

AC:

AN:

168056

Hom.:

AF XY:

0.000319

AC XY:

AN XY:

56388

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 SAS exome

AF:

0.0000640

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

Gnomad4 AFR exome

AF:

0.00272

Gnomad4 AMR exome

AF:

0.000322

Gnomad4 ASJ exome

AF:

0.0000535

Gnomad4 EAS exome

AF:

0.000901

Gnomad4 SAS exome

AF:

0.0000191

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.000176

GnomAD4 genome

AF:

0.000678

AC:

AN:

112025

Hom.:

Cov.:

AF XY:

0.000468

AC XY:

AN XY:

34207

show subpopulations

Gnomad4 AFR

AF:

0.00211

Gnomad4 AMR

AF:

0.000189

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00170

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00131

Alfa

AF:

0.000521

Hom.:

Bravo

AF:

0.000918

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 16, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

0.52

DANN

Benign

0.51

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over