chr3-196472332-TG-GC

Variant names:

• chr3-196472332-TG-GC
• NM_152617.4:c.1202_1203delCAinsGC
• RNF168 p.Pro401Arg

Variant summary

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

The NM_152617.4(RNF168):​c.1202_1203delCAinsGC​(p.Pro401Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P401Q) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNF168 NM_152617.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.44
• Publications: 0 publications found

Genes affected

RNF168 (HGNC:26661): (ring finger protein 168) This gene encodes an E3 ubiquitin ligase protein that contains a RING finger, a motif present in a variety of functionally distinct proteins and known to be involved in protein-DNA and protein-protein interactions. The protein is involved in DNA double-strand break (DSB) repair. Mutations in this gene result in Riddle syndrome. [provided by RefSeq, Sep 2011]

RNF168 Gene-Disease associations (from GenCC):

• RIDDLE syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152617.4. 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
	RNF168	NM_152617.4	MANE Select	c.1202_1203delCAinsGC	p.Pro401Arg	missense	N/A	NP_689830.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF168	ENST00000318037.3	TSL:1 MANE Select	c.1202_1203delCAinsGC	p.Pro401Arg	missense	N/A	ENSP00000320898.3	Q8IYW5
	RNF168	ENST00000437070.1	TSL:2	n.*774_*775delCAinsGC		non_coding_transcript_exon	Exon 5 of 5	ENSP00000396712.1	F8WD60
	RNF168	ENST00000437070.1	TSL:2	n.*774_*775delCAinsGC		3_prime_UTR	Exon 5 of 5	ENSP00000396712.1	F8WD60

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-196199203;