X-105908827-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_198465.4(NRK):​c.1186C>T​(p.Pro396Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000091 in 1,208,434 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 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 0.000018 ( 0 hom., 0 hem., cov: 23)
Exomes 𝑓: 0.0000082 ( 0 hom. 4 hem. )

Consequence

NRK
NM_198465.4 missense

Scores

1
5
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.73
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.40877652).
BS2
High Hemizygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NRKNM_198465.4 linkc.1186C>T p.Pro396Ser missense_variant Exon 13 of 29 ENST00000243300.14 NP_940867.2 Q7Z2Y5-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NRKENST00000243300.14 linkc.1186C>T p.Pro396Ser missense_variant Exon 13 of 29 1 NM_198465.4 ENSP00000434830.1 Q7Z2Y5-1
NRKENST00000428173.3 linkn.*1181C>T non_coding_transcript_exon_variant Exon 13 of 23 2 ENSP00000438378.2 F5H049
NRKENST00000428173.3 linkn.*1181C>T 3_prime_UTR_variant Exon 13 of 23 2 ENSP00000438378.2 F5H049

Frequencies

GnomAD3 genomes
AF:
0.0000179
AC:
2
AN:
111577
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
33755
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000191
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
GnomAD3 exomes
AF:
0.00000553
AC:
1
AN:
180769
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
67053
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000366
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000821
AC:
9
AN:
1096857
Hom.:
0
Cov.:
31
AF XY:
0.0000110
AC XY:
4
AN XY:
362335
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000852
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000595
Gnomad4 OTH exome
AF:
0.0000217
GnomAD4 genome
AF:
0.0000179
AC:
2
AN:
111577
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
33755
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000191
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000756

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 04, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1186C>T (p.P396S) alteration is located in exon 13 (coding exon 13) of the NRK gene. This alteration results from a C to T substitution at nucleotide position 1186, causing the proline (P) at amino acid position 396 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.25
BayesDel_addAF
Benign
-0.097
T
BayesDel_noAF
Benign
-0.27
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.23
T
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Benign
0.79
T
M_CAP
Pathogenic
0.44
D
MetaRNN
Benign
0.41
T
MetaSVM
Uncertain
-0.055
T
MutationAssessor
Benign
0.81
L
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-1.9
N
REVEL
Benign
0.26
Sift
Uncertain
0.0010
D
Sift4G
Benign
0.41
T
Polyphen
1.0
D
Vest4
0.23
MutPred
0.14
Gain of phosphorylation at P396 (P = 0.0146);
MVP
0.72
ClinPred
0.70
D
GERP RS
5.0
Varity_R
0.26
gMVP
0.34

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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.

Other links and lift over

dbSNP: rs917736775; hg19: chrX-105152819; API