13-78615769-T-G

Position:

• chr13-78615769-T-G

Variant summary

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

The NM_024546.4(OBI1):​c.1992A>C​(p.Glu664Asp) 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. 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)
• Consequence: OBI1 NM_024546.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.456

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

ACMG classification

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=0.054652065).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OBI1	NM_024546.4	c.1992A>C	p.Glu664Asp	missense_variant	6/6	ENST00000282003.7
OBI1-AS1	NR_047001.1	n.862T>G		non_coding_transcript_exon_variant	6/6
OBI1	XM_011535225.2	c.1761A>C	p.Glu587Asp	missense_variant	5/5
OBI1	XM_024449410.2	c.1761A>C	p.Glu587Asp	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OBI1	ENST00000282003.7	c.1992A>C	p.Glu664Asp	missense_variant	6/6	1	NM_024546.4	P1
OBI1-AS1	ENST00000560209.6	n.392T>G		non_coding_transcript_exon_variant	4/4	4
OBI1-AS1	ENST00000560584.2	n.666T>G		non_coding_transcript_exon_variant	4/4	5
OBI1-AS1	ENST00000606429.5	n.862T>G		non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 16, 2023

The c.1992A>C (p.E664D) alteration is located in exon 6 (coding exon 6) of the RNF219 gene. This alteration results from a A to C substitution at nucleotide position 1992, causing the glutamic acid (E) at amino acid position 664 to be replaced by an aspartic acid (D). 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	0.090
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.29
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.63	N
MutationTaster	Benign	0.53	N
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.10
Sift	Benign	0.064	T
Sift4G	Benign	0.36	T
Polyphen		0.0010	B
Vest4		0.11
MutPred		0.074		Gain of helix (P = 0.1736);
MVP		0.15
MPC		0.034
ClinPred		0.11	T
GERP RS		-0.044
Varity_R		0.039
gMVP		0.078

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: chr13-79189904;