Variant chr13-78616602-G-A 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.1159C>T(p.Pro387Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000508 in 1,614,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

OBI1
NM_024546.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.60

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=0.021121532).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
OBI1	NM_024546.4 linkuse as main transcript	c.1159C>T	p.Pro387Ser	missense_variant	6/6	ENST00000282003.7
OBI1-AS1	NR_047001.1 linkuse as main transcript	n.1695G>A		non_coding_transcript_exon_variant	6/6
OBI1	XM_011535225.2 linkuse as main transcript	c.928C>T	p.Pro310Ser	missense_variant	5/5
OBI1	XM_024449410.2 linkuse as main transcript	c.928C>T	p.Pro310Ser	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
OBI1	ENST00000282003.7 linkuse as main transcript	c.1159C>T	p.Pro387Ser	missense_variant	6/6	1	NM_024546.4	P1
OBI1-AS1	ENST00000560584.2 linkuse as main transcript	n.1499G>A		non_coding_transcript_exon_variant	4/4	5
OBI1-AS1	ENST00000606429.5 linkuse as main transcript	n.1695G>A		non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000915

AC:

AN:

251354

Hom.:

AF XY:

0.0000957

AC XY:

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.00129

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000322

AC:

AN:

1461872

Hom.:

Cov.:

AF XY:

0.0000316

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00116

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000993

GnomAD4 genome

AF:

0.000230

AC:

AN:

152298

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.000794

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000546

Hom.:

Bravo

AF:

0.000378

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000115

AC:

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

May 01, 2024

The c.1159C>T (p.P387S) alteration is located in exon 6 (coding exon 6) of the RNF219 gene. This alteration results from a C to T substitution at nucleotide position 1159, causing the proline (P) at amino acid position 387 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

0.23

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.044

Eigen

Benign

0.045

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.0025

MetaRNN

Benign

0.021

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

MutationTaster

Benign

0.76

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.4

REVEL

Benign

0.062

Sift

Benign

0.11

Sift4G

Benign

0.83

Polyphen

0.024

Vest4

0.18

MVP

0.34

MPC

0.040

ClinPred

0.015

GERP RS

5.1

Varity_R

0.037

gMVP

0.14

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