NM_198465.4:c.932C>T

Variant names:

• chrX-105906500-C-T
• NM_198465.4:c.932C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_198465.4(NRK):​c.932C>T​(p.Pro311Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: NRK NM_198465.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.31
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.885

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.932C>T	p.Pro311Leu	missense	Exon 11 of 29	NP_940867.2	Q7Z2Y5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRK	ENST00000243300.14	TSL:1 MANE Select	c.932C>T	p.Pro311Leu	missense	Exon 11 of 29	ENSP00000434830.1	Q7Z2Y5-1
	NRK	ENST00000882684.1		c.932C>T	p.Pro311Leu	missense	Exon 11 of 28	ENSP00000552743.1
	NRK	ENST00000882683.1		c.932C>T	p.Pro311Leu	missense	Exon 11 of 28	ENSP00000552742.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1040331 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 314093

African (AFR) AF: 0.00 AC: 0 AN: 25528

American (AMR) AF: 0.00 AC: 0 AN: 33701

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18534

East Asian (EAS) AF: 0.00 AC: 0 AN: 29459

South Asian (SAS) AF: 0.00 AC: 0 AN: 47285

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39496

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3970

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 798407

Other (OTH) AF: 0.00 AC: 0 AN: 43951

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.38	T
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.73	T
M_CAP	Pathogenic	0.52	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Benign	-0.69	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		7.3
PrimateAI	Benign	0.34	T
PROVEAN	Pathogenic	-7.1	D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.81	P
Vest4		0.48
MutPred		0.85		Loss of disorder (P = 0.106)
MVP		0.56
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.56
gMVP		0.76
Mutation Taster		=46/54	disease causing

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

Other links and lift over

hg19: chrX-105150493;