Variant chr13-78615677-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024546.4(OBI1):c.2084T>G(p.Val695Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

OBI1
NM_024546.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.30

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09174281).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
OBI1	NM_024546.4 linkuse as main transcript	c.2084T>G	p.Val695Gly	missense_variant	6/6	ENST00000282003.7
OBI1-AS1	NR_047001.1 linkuse as main transcript	n.770A>C		splice_region_variant, non_coding_transcript_exon_variant	6/6
OBI1	XM_011535225.2 linkuse as main transcript	c.1853T>G	p.Val618Gly	missense_variant	5/5
OBI1	XM_024449410.2 linkuse as main transcript	c.1853T>G	p.Val618Gly	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
OBI1	ENST00000282003.7 linkuse as main transcript	c.2084T>G	p.Val695Gly	missense_variant	6/6	1	NM_024546.4	P1
OBI1-AS1	ENST00000560209.6 linkuse as main transcript	n.300A>C		splice_region_variant, non_coding_transcript_exon_variant	4/4	4
OBI1-AS1	ENST00000560584.2 linkuse as main transcript	n.574A>C		splice_region_variant, non_coding_transcript_exon_variant	4/4	5
OBI1-AS1	ENST00000606429.5 linkuse as main transcript	n.770A>C		splice_region_variant, non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461778

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jun 07, 2023

The c.2084T>G (p.V695G) alteration is located in exon 6 (coding exon 6) of the RNF219 gene. This alteration results from a T to G substitution at nucleotide position 2084, causing the valine (V) at amino acid position 695 to be replaced by a glycine (G). 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

0.13

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.044

Eigen

Benign

-0.096

Eigen_PC

Benign

0.059

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.58

M_CAP

Benign

0.0086

MetaRNN

Benign

0.092

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

MutationTaster

Benign

1.0

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.3

REVEL

Benign

0.096

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.024

Polyphen

0.012

Vest4

0.32

MutPred

0.16

Loss of stability (P = 0.0148);

MVP

0.30

MPC

0.18

ClinPred

0.73

GERP RS

4.5

Varity_R

0.25

gMVP

0.23

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over