Variant 13-78616034-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024546.4(OBI1):c.1727T>C(p.Phe576Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000192 in 1,614,156 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00019 ( 1 hom. )

Consequence

OBI1
NM_024546.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.52

Variant links:

Genes affected

OBI1 (HGNC:20308): (ORC ubiquitin ligase 1) Enables chromatin binding activity and ubiquitin-protein transferase activity. Involved in protein autoubiquitination; protein monoubiquitination; and regulation of DNA replication. Located in chromatin. [provided by Alliance of Genome Resources, Apr 2022]

OBI1 links:

OBI1-AS1 (HGNC:42700): (OBI1 antisense RNA 1)

OBI1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.043555886).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
OBI1	NM_024546.4 linkuse as main transcript	c.1727T>C	p.Phe576Ser	missense_variant	6/6	ENST00000282003.7
OBI1-AS1	NR_047001.1 linkuse as main transcript	n.1127A>G		non_coding_transcript_exon_variant	6/6
OBI1	XM_011535225.2 linkuse as main transcript	c.1496T>C	p.Phe499Ser	missense_variant	5/5
OBI1	XM_024449410.2 linkuse as main transcript	c.1496T>C	p.Phe499Ser	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
OBI1	ENST00000282003.7 linkuse as main transcript	c.1727T>C	p.Phe576Ser	missense_variant	6/6	1	NM_024546.4	P1
OBI1-AS1	ENST00000560584.2 linkuse as main transcript	n.931A>G		non_coding_transcript_exon_variant	4/4	5
OBI1-AS1	ENST00000606429.5 linkuse as main transcript	n.1127A>G		non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes

AF:

0.000177

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000318

AC:

AN:

251186

Hom.:

AF XY:

0.000449

AC XY:

AN XY:

135790

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00124

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000317

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000194

AC:

283

AN:

1461834

Hom.:

Cov.:

AF XY:

0.000248

AC XY:

180

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00121

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000133

Gnomad4 OTH exome

AF:

0.000265

GnomAD4 genome

AF:

0.000177

AC:

AN:

152322

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.000140

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000379

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.000771

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 20, 2021

The c.1727T>C (p.F576S) alteration is located in exon 6 (coding exon 6) of the RNF219 gene. This alteration results from a T to C substitution at nucleotide position 1727, causing the phenylalanine (F) at amino acid position 576 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.027

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.69

M_CAP

Benign

0.022

MetaRNN

Benign

0.044

MetaSVM

Benign

-1.2

MutationAssessor

Benign

0.90

MutationTaster

Benign

1.0

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.69

REVEL

Benign

0.15

Sift

Uncertain

0.0020

Sift4G

Benign

0.51

Polyphen

1.0

Vest4

0.47

MVP

0.49

MPC

0.16

ClinPred

0.047

GERP RS

5.9

Varity_R

0.27

gMVP

0.11

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over