X-105888377-A-G

Variant names:

• chrX-105888377-A-G
• NM_198465.4:c.336A>G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_198465.4(NRK):​c.336A>G​(p.Ala112Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: NRK NM_198465.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.730

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

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant X-105888377-A-G is Benign according to our data. Variant chrX-105888377-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2661125.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.73 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRK	NM_198465.4	c.336A>G	p.Ala112Ala	synonymous_variant	Exon 5 of 29	ENST00000243300.14	NP_940867.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRK	ENST00000243300.14	c.336A>G	p.Ala112Ala	synonymous_variant	Exon 5 of 29	1	NM_198465.4	ENSP00000434830.1
NRK	ENST00000536164.5	c.336A>G	p.Ala112Ala	synonymous_variant	Exon 5 of 7	1		ENSP00000438785.1
NRK	ENST00000428173.3	n.336A>G		non_coding_transcript_exon_variant	Exon 5 of 23	2		ENSP00000438378.2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 23

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

NRK: PM2:Supporting, BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	7.1
DANN	Benign	0.73

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-105132370;