chr3-196487566-G-C

Variant names:

• chr3-196487566-G-C
• NM_152617.4:c.391C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152617.4(RNF168):​c.391C>G​(p.Arg131Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RNF168 NM_152617.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.52

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF168	NM_152617.4	c.391C>G	p.Arg131Gly	missense_variant	Exon 3 of 6	ENST00000318037.3	NP_689830.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF168	ENST00000318037.3	c.391C>G	p.Arg131Gly	missense_variant	Exon 3 of 6	1	NM_152617.4	ENSP00000320898.3
RNF168	ENST00000437070.1	n.314C>G		non_coding_transcript_exon_variant	Exon 2 of 5	2		ENSP00000396712.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.1	M
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.13
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.014	D
Polyphen		1.0	D
Vest4		0.64
MutPred		0.21		Gain of glycosylation at S134 (P = 0.0014);
MVP		0.67
MPC		0.46
ClinPred		0.98	D
GERP RS		2.6
Varity_R		0.59
gMVP		0.38

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: chr3-196214437;