X-105908283-G-T

Variant names:

• chrX-105908283-G-T
• rs55862725
• NM_198465.4:c.1065G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198465.4(NRK):​c.1065G>T​(p.Gln355His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000103 in 966,299 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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000010 (0 hom. 1 hem.)
• Consequence: NRK NM_198465.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.508
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.080130994).

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.1065G>T	p.Gln355His	missense	Exon 12 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.1065G>T	p.Gln355His	missense	Exon 12 of 29	ENSP00000434830.1	Q7Z2Y5-1
	NRK	ENST00000882684.1		c.1065G>T	p.Gln355His	missense	Exon 12 of 28	ENSP00000552743.1
	NRK	ENST00000882683.1		c.1065G>T	p.Gln355His	missense	Exon 12 of 28	ENSP00000552742.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000103 AC: 1 AN: 966299 Hom.: 0 Cov.: 18 AF XY: 0.00000362 AC XY: 1 AN XY: 276153

African (AFR) AF: 0.0000463 AC: 1 AN: 21588

American (AMR) AF: 0.00 AC: 0 AN: 23498

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17110

East Asian (EAS) AF: 0.00 AC: 0 AN: 25974

South Asian (SAS) AF: 0.00 AC: 0 AN: 42415

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37237

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 753620

Other (OTH) AF: 0.00 AC: 0 AN: 41103

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.51
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.063
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.0020	B
Vest4		0.24
MutPred		0.17		Loss of MoRF binding (P = 0.1156)
MVP		0.21
ClinPred		0.42	T
GERP RS		0.23
Varity_R		0.36
gMVP		0.28
Mutation Taster		=98/2	polymorphism

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

dbSNP: rs55862725; hg19: chrX-105152275;