X-105906508-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198465.4(NRK):​c.940C>T​(p.Arg314Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000867 in 1,153,409 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict 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: 22)
Exomes 𝑓: 0.0000077 ( 0 hom. 1 hem. )

Consequence

NRK
NM_198465.4 missense

Scores

2
4
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0460
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.14776969).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NRKNM_198465.4 linkc.940C>T p.Arg314Trp missense_variant Exon 11 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.940C>T p.Arg314Trp missense_variant Exon 11 of 29 1 NM_198465.4 ENSP00000434830.1 Q7Z2Y5-1
NRKENST00000428173.3 linkn.940C>T non_coding_transcript_exon_variant Exon 11 of 23 2 ENSP00000438378.2 F5H049

Frequencies

GnomAD3 genomes
AF:
0.0000184
AC:
2
AN:
108621
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
AN XY:
31287
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:
0.0000382
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000766
AC:
8
AN:
1044788
Hom.:
0
Cov.:
22
AF XY:
0.00000313
AC XY:
1
AN XY:
319994
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.00000994
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000184
AC:
2
AN:
108621
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
AN XY:
31287
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000382
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000264

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jun 19, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.940C>T (p.R314W) alteration is located in exon 11 (coding exon 11) of the NRK gene. This alteration results from a C to T substitution at nucleotide position 940, causing the arginine (R) at amino acid position 314 to be replaced by a tryptophan (W). 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
0.12
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.75
CADD
Benign
14
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.48
T
FATHMM_MKL
Benign
0.085
N
LIST_S2
Uncertain
0.91
D
M_CAP
Uncertain
0.10
D
MetaRNN
Benign
0.15
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.55
N
PrimateAI
Benign
0.21
T
PROVEAN
Pathogenic
-6.1
D
REVEL
Benign
0.10
Sift
Benign
0.048
D
Sift4G
Pathogenic
0.0010
D
Polyphen
0.0040
B
Vest4
0.22
MVP
0.41
ClinPred
0.31
T
GERP RS
3.5
Varity_R
0.17
gMVP
0.57

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

LitVar

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

Other links and lift over

dbSNP: rs747023598; hg19: chrX-105150501; COSMIC: COSV54589969; API