3-196472007-G-A

Position:

• chr3-196472007-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_152617.4(RNF168):​c.1528C>T​(p.Pro510Ser) variant causes a missense 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNF168 NM_152617.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.389

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.043632746).
• BP6: Variant 3-196472007-G-A is Benign according to our data. Variant chr3-196472007-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2230149.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF168	NM_152617.4	c.1528C>T	p.Pro510Ser	missense_variant	6/6	ENST00000318037.3	NP_689830.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF168	ENST00000318037.3	c.1528C>T	p.Pro510Ser	missense_variant	6/6	1	NM_152617.4	ENSP00000320898.3
RNF168	ENST00000437070.1	n.*1100C>T		non_coding_transcript_exon_variant	5/5	2		ENSP00000396712.1
RNF168	ENST00000437070.1	n.*1100C>T		3_prime_UTR_variant	5/5	2		ENSP00000396712.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 17, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.15
DANN	Benign	0.12
DEOGEN2	Benign	0.0014	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.088	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.99	L
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.30	N
REVEL	Benign	0.038
Sift	Benign	0.74	T
Sift4G	Benign	1.0	T
Polyphen		0.0020	B
Vest4		0.040
MutPred		0.15		Gain of glycosylation at S514 (P = 0.0062);
MVP		0.27
MPC		0.069
ClinPred		0.024	T
GERP RS		1.1
Varity_R		0.020
gMVP		0.058

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: chr3-196198878; COSMIC: COSV58839412; COSMIC: COSV58839412;